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Dra Clarisa MaxitSub Jefe Servicio de Neurologiacutea Infantil
Hospital Italiano de Buenos Aires
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SSTAT SEREFRACTORIO
5 MIN 30 MIN
STATUS
ESTABLECIDO
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS y otros
El tratamiento precoz de las crisis previene el efecto kindlingEl tratamiento precoz previene la injuria neuronal
El tto pre‐hospitalario es importante 182 chicos con SE convulsivopor cada minuto de retraso del inicio del tratamiento desde el inicio del SE hay un aumento de riesgo acumulativo del 5 en que el SE dure maacutes de 60 minutos
Chin RF Peckman C et alLancet Neurol 2008
Los nintildeos que reciben el 3er AE dentro de la hora de tto regresaron a la liacutenea base en forma significativa maacutes frecuente que aquellos con administracioacuten maacutes tardiacutea (81 vs 0)
Lambrechtsen FA Buchhalter JEpilepsia 2008
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
benzodiacepinasSon efectivas cuando son utilizadas al inicio de las crisisHay cambios en el receptor GABA que modifican la respuesta subsecuente luego de varios minutos iniciada la crisisDiazepam VS lorazepam VS midazolam
Lorazepam
El lorazepam ev presenta mayor eficacia y disminuye el tiempo de crisis comparado con el diazepam ev
Alldrredge Bk et al N England J Med 2001
Requiere refrigeracioacuten manejo SEAdministracioacuten IV Hospitalario
midazolamEs una imidazobenzodiacepina A pH 4 es un anillo abierto que es soluble en aguaA pH fisioloacutegico el anillo se cierra y se hace muy liposoluble permitiendo una rapida penetrancia cerebralMidazolam bucal intranasalIM 015 a 05 mgkg
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SSTAT SEREFRACTORIO
5 MIN 30 MIN
STATUS
ESTABLECIDO
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS y otros
El tratamiento precoz de las crisis previene el efecto kindlingEl tratamiento precoz previene la injuria neuronal
El tto pre‐hospitalario es importante 182 chicos con SE convulsivopor cada minuto de retraso del inicio del tratamiento desde el inicio del SE hay un aumento de riesgo acumulativo del 5 en que el SE dure maacutes de 60 minutos
Chin RF Peckman C et alLancet Neurol 2008
Los nintildeos que reciben el 3er AE dentro de la hora de tto regresaron a la liacutenea base en forma significativa maacutes frecuente que aquellos con administracioacuten maacutes tardiacutea (81 vs 0)
Lambrechtsen FA Buchhalter JEpilepsia 2008
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
benzodiacepinasSon efectivas cuando son utilizadas al inicio de las crisisHay cambios en el receptor GABA que modifican la respuesta subsecuente luego de varios minutos iniciada la crisisDiazepam VS lorazepam VS midazolam
Lorazepam
El lorazepam ev presenta mayor eficacia y disminuye el tiempo de crisis comparado con el diazepam ev
Alldrredge Bk et al N England J Med 2001
Requiere refrigeracioacuten manejo SEAdministracioacuten IV Hospitalario
midazolamEs una imidazobenzodiacepina A pH 4 es un anillo abierto que es soluble en aguaA pH fisioloacutegico el anillo se cierra y se hace muy liposoluble permitiendo una rapida penetrancia cerebralMidazolam bucal intranasalIM 015 a 05 mgkg
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
El tratamiento precoz de las crisis previene el efecto kindlingEl tratamiento precoz previene la injuria neuronal
El tto pre‐hospitalario es importante 182 chicos con SE convulsivopor cada minuto de retraso del inicio del tratamiento desde el inicio del SE hay un aumento de riesgo acumulativo del 5 en que el SE dure maacutes de 60 minutos
Chin RF Peckman C et alLancet Neurol 2008
Los nintildeos que reciben el 3er AE dentro de la hora de tto regresaron a la liacutenea base en forma significativa maacutes frecuente que aquellos con administracioacuten maacutes tardiacutea (81 vs 0)
Lambrechtsen FA Buchhalter JEpilepsia 2008
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
benzodiacepinasSon efectivas cuando son utilizadas al inicio de las crisisHay cambios en el receptor GABA que modifican la respuesta subsecuente luego de varios minutos iniciada la crisisDiazepam VS lorazepam VS midazolam
Lorazepam
El lorazepam ev presenta mayor eficacia y disminuye el tiempo de crisis comparado con el diazepam ev
Alldrredge Bk et al N England J Med 2001
Requiere refrigeracioacuten manejo SEAdministracioacuten IV Hospitalario
midazolamEs una imidazobenzodiacepina A pH 4 es un anillo abierto que es soluble en aguaA pH fisioloacutegico el anillo se cierra y se hace muy liposoluble permitiendo una rapida penetrancia cerebralMidazolam bucal intranasalIM 015 a 05 mgkg
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
El tto pre‐hospitalario es importante 182 chicos con SE convulsivopor cada minuto de retraso del inicio del tratamiento desde el inicio del SE hay un aumento de riesgo acumulativo del 5 en que el SE dure maacutes de 60 minutos
Chin RF Peckman C et alLancet Neurol 2008
Los nintildeos que reciben el 3er AE dentro de la hora de tto regresaron a la liacutenea base en forma significativa maacutes frecuente que aquellos con administracioacuten maacutes tardiacutea (81 vs 0)
Lambrechtsen FA Buchhalter JEpilepsia 2008
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
benzodiacepinasSon efectivas cuando son utilizadas al inicio de las crisisHay cambios en el receptor GABA que modifican la respuesta subsecuente luego de varios minutos iniciada la crisisDiazepam VS lorazepam VS midazolam
Lorazepam
El lorazepam ev presenta mayor eficacia y disminuye el tiempo de crisis comparado con el diazepam ev
Alldrredge Bk et al N England J Med 2001
Requiere refrigeracioacuten manejo SEAdministracioacuten IV Hospitalario
midazolamEs una imidazobenzodiacepina A pH 4 es un anillo abierto que es soluble en aguaA pH fisioloacutegico el anillo se cierra y se hace muy liposoluble permitiendo una rapida penetrancia cerebralMidazolam bucal intranasalIM 015 a 05 mgkg
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
benzodiacepinasSon efectivas cuando son utilizadas al inicio de las crisisHay cambios en el receptor GABA que modifican la respuesta subsecuente luego de varios minutos iniciada la crisisDiazepam VS lorazepam VS midazolam
Lorazepam
El lorazepam ev presenta mayor eficacia y disminuye el tiempo de crisis comparado con el diazepam ev
Alldrredge Bk et al N England J Med 2001
Requiere refrigeracioacuten manejo SEAdministracioacuten IV Hospitalario
midazolamEs una imidazobenzodiacepina A pH 4 es un anillo abierto que es soluble en aguaA pH fisioloacutegico el anillo se cierra y se hace muy liposoluble permitiendo una rapida penetrancia cerebralMidazolam bucal intranasalIM 015 a 05 mgkg
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
benzodiacepinasSon efectivas cuando son utilizadas al inicio de las crisisHay cambios en el receptor GABA que modifican la respuesta subsecuente luego de varios minutos iniciada la crisisDiazepam VS lorazepam VS midazolam
Lorazepam
El lorazepam ev presenta mayor eficacia y disminuye el tiempo de crisis comparado con el diazepam ev
Alldrredge Bk et al N England J Med 2001
Requiere refrigeracioacuten manejo SEAdministracioacuten IV Hospitalario
midazolamEs una imidazobenzodiacepina A pH 4 es un anillo abierto que es soluble en aguaA pH fisioloacutegico el anillo se cierra y se hace muy liposoluble permitiendo una rapida penetrancia cerebralMidazolam bucal intranasalIM 015 a 05 mgkg
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Lorazepam
El lorazepam ev presenta mayor eficacia y disminuye el tiempo de crisis comparado con el diazepam ev
Alldrredge Bk et al N England J Med 2001
Requiere refrigeracioacuten manejo SEAdministracioacuten IV Hospitalario
midazolamEs una imidazobenzodiacepina A pH 4 es un anillo abierto que es soluble en aguaA pH fisioloacutegico el anillo se cierra y se hace muy liposoluble permitiendo una rapida penetrancia cerebralMidazolam bucal intranasalIM 015 a 05 mgkg
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
midazolamEs una imidazobenzodiacepina A pH 4 es un anillo abierto que es soluble en aguaA pH fisioloacutegico el anillo se cierra y se hace muy liposoluble permitiendo una rapida penetrancia cerebralMidazolam bucal intranasalIM 015 a 05 mgkg
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
midazolamEl midazolam por viacutea NO IV acelera la finalizacioacuten de las crisisLa utilizacioacuten de midazolam IM o IN vs Diazepam IV presentaban eficacia similar de finalizacioacuten de crisis pero el midazolam presento una diferencia fija de 3 minutos
RAMPART Trial ndash Michigan UniversitySilbergleit R and Lowestein Dan
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
midazolam
Dan Milikan Robert SilbergleitEmerg Med Clin N AM 2009
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
midazolam
Danie l P WemwlingNeurotherapeutics A bil 2009
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Midazolam IM vs IN vs IV
Danie l P WemwlingNeurotherapeutics Abril 2009
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOSDCIGTPM
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Hay que tener un plan
Todas la unidades deben contar con un protocolo escrito del tratamiento farmacoloacutegico del SE y este protocolo debe estar claramente estadificado y estructurado por tiempo
Consenso Europeo Tratamiento del Status Epilepticus ‐ Londres 2008
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
542 pacientes pediaacutetricos estudio multiceacutentrico Manejo emergencia del SE convulsivoEn el DE la mediana de tiempo para administrar el 2do faacutermaco fue de 24 minutos
Acworth J Lewena SPediatr Emerg Care 2009
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Drug management for acute tonic-clonic convulsions including convulsive status epilepticus in children
Appleton R Macleod S Martland TRoald DahlEEG Unit Alder Hey Childrens Hospital Eaton Road Liverpool
OBJECTIVES To review the evidence comparing the efficacy and safety of midazolam diazepam lorazepam phenobarbitone phenytoin and paraldehyde in treating acute tonic-clonic convulsions and convulsive status
epilepticus in children treated in hospitalSEARCH STRATEGY We searched the Cochrane Epilepsy Groups Specialized Register (1st July 2007) the
Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 3 2007) and MEDLINE (1966 to July 2007) SELECTION CRITERIA Randomized and quasi-randomized controlled trials
comparing any anticonvulsant drugs used for the treatment of an acute tonic-clonic convulsion including convulsive status epilepticus in children DATA COLLECTION AND ANALYSIS Two review authors
independently assessed trials for inclusion and extracted data MAIN RESULTS Four trials involving 383 participants were included(1) Intravenous lorazepam is as effective as intravenous diazepam in the treatment of acute tonic clonic convulsions 1927 (70) versus 2234 (65) RR 109 (95 CI 077 to 154) has fewer adverse events and rectal lorazepam may be more effective than rectal diazepam 66 versus 619 (31) RR 317 (95 CI 163 to 614)(2) Buccal midazolam controlled seizures in 61109 (56) compared with 30110
(27) of rectal diazepam treated episodes with acute tonic-clonic convulsions RR 205 ( 95 CI 145 to 291)(3) Intranasal midazolam is as effective as intravenous diazepam in the treatment of prolonged febrile
convulsions 2326 (88) versus 2426 (92) RR 096 (95 CI 08 to 114)(4)AUTHORS CONCLUSIONS The conclusions of this update have changed to suggest that intravenous
lorazepam is at least as effective as intravenous diazepam and is associated with fewer adverse events in the treatment of acute tonic-clonic convulsions Where intravenous access is unavailable there is evidence from
one trial that buccal midazolam is the treatment of choiceCochrane Database Syst Rev 2008 Jul 16(3)CD001905
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Acido Valproico (VPA) Levetiracetam (LEV)
Baja unioacuten a proteiacutenasCineacutetica linealLVT bajo metabolismo hepaacutetico y pocas interacciones VPA metabolismo microsomal y muchas interacciones
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Acido valproico20 estudios publicados 533 adultos y nintildeosTodos mostraron efectividad similar a la DFH en pacientes que NO respondieron a las benzodiacepinas o como primea liacutenea de ttoDosis usual 15 a 45 mg kg en bolo (6mgkgmin) seguido de infusioacuten 1 a 5mgkghoraEfectos adversos menos del 10
hipotensioacuten plaquetopenia mareo
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
LevetiracetamAntiepileptico de amplio espectro
‐ Inhibe canales de calcio voltaje dependiente‐ facilita la inhibicioacuten gabaergica al desplazar moduladores negativos
‐ Reduce las corrientes tardiacuteas de potasio ‐ Presenta unioacuten a proteiacutenas sinaacutepticas que modulan la liberacioacuten de neurotransmisores
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Levetiracetam (LEV)Disponible IV en forma reciente Dosis de carga 20 mgKg IVBiodisponibilidad y bioequivalencia probadasNo hay estudios controladosControl referido del 31 al 100 de pacientesEfectos adversos somnolencia agresividad plaquetopeniaSE debe ajustar la dosis en la falla renal
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
J Child Neurol 2010 May25(5)551-5Intravenous levetiracetam in children with seizures a prospective safety studyNg YT Hastriter EV Cardenas JF Khoury EM Chapman KE Department of Pediatric Neurology Barrow Neurological Institute Phoenix Arizona 85013 USAAbstractIn 2006 intravenous levetiracetam received US Food and Drug Administration (FDA) approval for adjunctive treatment of partial onset seizures in adults with epilepsy 16 years or older We have established the safety tolerability and dosage of intravenous levetiracetam in children This prospective study included 30 children (6 months to lt15 years of age) Patients were administered a single dose of intravenous levetiracetam (50 mgkg maximal dose 2500 mg) over 15 minutes A blood level of levetiracetam was performed 10 minutes after the infusion The treated childrens average age was 63 years (range 05-148 years) The mean levetiracetam level was 833 microgmL (range 47-128 microgmL) There were no serious adverse reactions Minor reactions included sleepiness fatigue and restlessness An apparent decrease in seizure frequency across all seizure types was noted The dose of 50 mgkg was well tolerated by the patients and is a safe appropriate loading dose
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
FASES DEL STATUS EPILEPTICUS
SEINMINENTE
SEREFRACTORIO
SEESTABLECIDO
5 MIN 30 MIN
UNIDAD DE CUIDADOS INTENSIVOSPRE HOSPITALARIO GUARDIA
BZD AE ANESTESICOS
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Manejo del status epilepticus
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Lorazepam IV
Diazepam IV
Lorazepam iv
Midazolam bucal INIM
Midazolam IV
Lorazepam IV
Diazepam IV DFH LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
midazolamMetanalisis 111 nintildeos SER fue efectiva como otras drogas inductoras de coma con menor mortalidad
Gilbert DL Glauser TA Jchild Neurol 199940 nintildeos midazolam vs diazepam IV eficacia similar midazolam recurrencia mayor (57 vs 16)
Singhi S et al J Child Neurol 2002EA desaturaciones transitorias hipotensioacuten arterial
Midazolam bolo inicial 01 mgkg con infusioacuten posterior 1 a 2 Microgramokgmi hasta 30microgramoskgmin
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Rev Neurol (Paris) 2010 Jun-Jul166(6-7)648-52 [Use of midazolam for refractory status epilepticus in children]Lampin ME Dorkenoo A Lamblin MD Botte A Leclerc F Auvin S Service de reacuteanimation peacutediatrique CHRU de Lille Lille cedex FranceMETHODSThis was a retrospective analysis of 29 children admitted to the Lille University Hospital pediatric intensive care unit (PICU) for RSE between May 2006 and July 2008 The onset of the study corresponded with a new therapeutic protocol applied in the PICU for RSE where midazolam was proposed as the first-line treatment (bolus ten continuous infusion until control) to be replaced by thiopenthal in case of failureRESULTSWe recorded 29 patients with RSE during the study period 26 were treated with midazolam including two where midazolam replaced thiopenthal because of hypotension Midazolam successfully controlled RSE in 58 of patients Mean delay to cessation of RSE was 48+-65 minutes Hypotension was observed in 8 of midazolam-treated patients and 71 of thiopenthal-treated patients Overall mortality was 15 (426) Two deaths occurred long after the cessation of RSE None of the deaths occurred in midazolam-treated patientsCONCLUSIONMidazolam is an efficient treatment for RSE in children Morbidity and mortality appear to be lower with midazolam compared with other antiepileptic drugs used for the treatment of RSE
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
FENOBARBITALEl fenobarbital a altas dosis hasta maacuteximo de 120 mgkg es una opcioacuten en el manejo del SERMenos inestabilidad hemodinaacutemica iacuteleo e infeccionesDosis repetidas de bolos de 10 mgkg cada 30 minutos sin maacuteximo nivel predeterminadoEl efecto sedante y depresor respiratorio se van tolerando no asiacute el efecto anticonvulsivante
Crawford TO et al Neurology 1988Lee WK Pediatr Neurol 2006
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Drogas nuevasTopiramatoLacosamida
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
TopiramatoMecanismo de accioacuten aumento de la funcioacuten inhibitoria del receptor GABA a inhibicioacuten de los receptores excitatorios AMPA bloqueo de los canales de Ca y Na e inhibicioacuten de la anhidrasa carboacutenicaVarios casos reportados en SE Refractario de buena tolerancia y efectividad administrado por SNG (3 a 10 mgkgdia)Inicio de efecto luego de 12 a 48hsPapel tardiacuteo en el SE en la salida del coma farmacoloacutegico
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
LacosamidaAumenta la inactivacioacuten lenta de los canales de sodioFormula viacutea oral e IV
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
anesteacutesicos
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Dieta cetogeacutenica
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Teatment of malignant refractory status epilepticus with ketogenic diet 5 case reportsAutores Autores Vaccarezza M Aberastury M Silva W Maxit C Marchione D Agosta G Child Neurology Child Neurology DepartmentDepartment Hospital Italiano de Buenos AiresHospital Italiano de Buenos Aires
Introduction Refractory status epilepticus (RSE) is a life-threatening condition defined as ongoing intermittent or continuous status epilepticus despite the administration of adequate doses of two standard intravenous anticonvulsant drugs It can last days weeks regardless of an adequate treatment with numerous antiepileptic drugs includi This condition is called malignant status epilepticus (MSE) Many therapeutic approaches have been documented for these patients such as intravenous valproic acid pentobarbital induced coma high dose phenobarbital midazolam and propofol
Ketogenic diet is a safe and effective alternative treatment for patients with refractory epilepsy when epilepsy surgery is not an option There are no studies of the use of ketogenic diet in refractory status epilepticus and we found isolated case reports in the literature
In this study we report five consecutive patients in a 4 year period with a malignant status epilepticus that lasted more than 5 days and receive ketogenic diet as treatment after failure with other more conventional treatment options
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
DISCUSION
We present a series of 5 patients with malignant status epileacutepticus In 4 patients the KD was effective in aborting the MSE where other antiepileptic drugs had failed including burst suppression coma The etiology of the SE differed between the patients The main cause was encephalitis (acute symptomatic) in three patients and 2 patients had chronic epilepsy (remote symptomatic) The 3 patients with encephalitis had a better outcomeAs ketosis can easily be achieved with fasting and that it was effective in aborting MSE in a high percentage of our patients we recommend to include the ketogenic diet in the treatment protocol for MSE It is relatively easy and safe to fast patients in the ICU after the patient has a diagnosis of MSE One of the patients with encephalitis became seizure free 24 hs after introducing KD The other three patients have a refractory epilepsy and one patient with a a previous chronic epilepsy died
CONCLUSIONKD can be easily introduced in patients in the ICU with an initial fasting phase followed by a 41 ratio These results support the potential efficacy and safety of KD for children with MSE where many other antiepileptic have failed
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Tratamiento inmunoloacutegicoHay casos de status epilepticus refractario que son inmunomediadosSe debe considerar la terapia inmune en pacientes con status epilepticus refractario de origen incierto o asociado a anticuerposSe utiliza gamaglobulina metilprednisolona plasmaferesis
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Protocolo acelerado del Manejo del SE
5 min30 min
PreHospitalario Unidad de Cuidados intensivosDepartamento emergencia
Diazepam IR
Midazolam bucal INIM
Lorazepam IV DFH
LEV IV Fenobarbital20 mgkg
VPA IVMidazolamIV goteo
tiopental
propofol
ketamina
Dietacetogenica
REFRACTARIOESTABLECIDOINMINENTE
IG IV
TOPIRAMATO
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
conclusionesEl tto de las crisis DEBE comenzar a los 5 minutos de iniciadaLa 1ra liacutenea de tto prehospitalaria incluye al DZP (IR) Midazolam (IM IN Bucal)La 1ra liacutenea de tto en el DE es el DZP LZP EV Se sugiere dosis de carga de DFH si se utiliza DZPSe diagnostica status epilepticus refractario luego del fracaso a la primera liacutenea de tto la eleccioacuten de la medicacioacuten dependeraacute de la disponibilidad capacidad del centro y el estado hemodinaacutemico
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
conclusionesEl acido valproico seriacutea una opcioacuten de tratamiento en el SE EstablecidoEl fenobarbital a altas dosis es una alternativa al tiopental en el SERLa dieta cetogeacutenica es una medida terapeacuteutica no farmacoloacutegica efectiva ante la recurrencia luego del coma farmacoloacutegicoConsiderar tratamiento inmunoloacutegico en el SER sin etiologiacutea clara
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Acad Emerg Med 2010 Jun17(6)575-82Midazolam versus diazepam for the treatment of status epilepticus in children and young adults a meta-analysisMcMullan J Sasson C Pancioli A Silbergleit R SourceDepartment of Emergency Medicine University of Cincinnati Cincinnati OH USA mcmulljWe performed a search of PubMed Web of Knowledge Embase Cochrane Database of Systematic Reviews Database of Abstracts of Reviews of Effectsfor studies published January 1 1950 through July 4 2009 English language quasi-experimental or randomized controlled trials comparing midazolam and diazepam as first-line treatment for SE and meeting the Consolidated Standards of Reporting Trials (CONSORT)-based quality measures were eligible Two reviewers independently screened studies for inclusion and extracted outcomes data Administration routes were stratified as non-IV (buccal intranasal intramuscular rectal) or IV Fixed-effects models generated pooled statisticsOBJECTIVESThe objective was to determine by systematic review if nonintravenous (non-IV) midazolam is as effective as diazepam by any route in terminating SE seizures in children and adults Time to seizure cessation and respiratory complications was examined
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
RESULTSSix studies with 774 subjects were included For seizure cessation midazolam by any route was superior to diazepam by any route (relative risk [RR] = 152 95 confidence interval [CI] = 127 to 182) Non-IV midazolam is as effective as IV diazepam (RR = 079 95 CI = 019 to 336) and buccal midazolam is superior to rectal diazepam in achieving seizure control (RR = 154 95 CI = 129 to 185) Midazolam was administered faster than diazepam (mean difference = 246 minutes 95 CI = 152 to 339 minutes) and had similar times between drug administration and seizure cessation Respiratory complications requiring intervention were similar regardless of administration route (RR = 149 95 CI = 025 to 872)CONCLUSIONSNon-IV midazolam compared to non-IV or IV diazepam is safe and effective in treating SE Comparison to lorazepam evaluation in adults and prospective confirmation of safety and efficacy is needed
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
Eur J Paediatr Neurol 2010 Mar14(2)162-8Lorazepam versus diazepam-phenytoin combination in the treatment of convulsive status epilepticus in children a randomized controlled trialSreenath TG Gupta P Sharma KK Krishnamurthy S SourceDepartment of Pediatrics University College of Medical Sciences and Guru Tegh Bahadur Hospital IndiaAbstractOBJECTIVETo determine whether intravenous lorazepam is as efficacious as diazepam-phenytoin combination in the treatment of convulsive status epilepticus in childrenSTUDY DESIGNRandomized controlled trialMETHODSA total of 178 children were enrolled in the study 90 in the lorazepam group and 88 in the diazepam-phenytoin combination group Enrolled subjects were between 1 and 12 years with a clinical diagnosis of convulsive status epilepticus presenting in pediatric emergency of a tertiary care hospital They were randomized to receive either intravenous lorazepam (01 mgkg) or intravenous diazepam (02 mgkg)-phenytoin (18 mgkg) combination at admission and were followed up for subsequent 18 h
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus
RESULTSThe overall success rate of therapy was 100 in both the groups There was no statistically significant difference in the two groups (lorazepam versus diazepam-phenytoin combination) in the median time taken to stop the seizure [20s in both groups] the number of subjects requiring more than one dose of the study drug to stop the presenting seizure [lorazepam 6(67) versus diazepam-phenytoin combination 14 (159) adjusted RR (95 CI)=0377 (0377 1046) P=0061] and the number () of patients having respiratory depression [lorazepam 4(44) versus diazepam-phenytoin combination 5 (56)] None of the patients in the two groups required additional anticonvulsant drug to stop the presenting seizure No patient required mechanical ventilation and none of the patients in the two groups required cross-over to the alternative regimenCONCLUSIONLorazepam is as efficacious and safe as diazepam-phenytoin combination We recommend use of lorazepam as a single drug to replace the two drug combination of diazepam-phenytoin combination to control the initial seizure in pediatric convulsive status epilepticus