the seizing patient

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The Seizing Patient

The Seizing PatientAbdul Aziz Al SibaniR 1ObjectiveTo know the causes and classification of seizure How to approach a seizing patient Management of seizing pt Case scenariosSeizure caused by toxins Seizure in pregnancyFebrile aizure IntroductionA seizure is the clinical manifestation of excessive, abnormal cortical neuronal activity.Primary vs secondary (reactive)Generalized vs partial

Reactive seizures in adultsSeizures caused by metabolic derangementSeizures caused by infectious diseases Seizures caused by drugs and toxins Seizures caused by traumaSeizures associated with malignancy or vasculitis Seizures caused by strokes, AVM and migrainesSeizures caused by degenerative disease of the CNS Gestational seizure

Status epilepticus Serial seizure activity without interictal recovery or prolonged, continuous seizure activity.Overall 30 day mortality for patients with generalized status epilepticus was 19-27%The most common cause of status epilepticus is discontinuation of AEM.ETIOLOGY OF STATUS EPILEPTICUS: COMMON CAUSATIVE DISORDERSMetabolic Disturbances Hepatic encephalopathy Hypocalcemia Hypoglycemia or hyperglycemia Hyponatremia Uremia

Infectious Processes CNS abscess Encephalitis MeningitisIntoxication Bupropion Camphor Clozapine Cyclosporine Flumazenil Fluoroquinolones Imipenem Isoniazid Lead Lidocaine Lithium Metronidazole Theophylline Tricyclic antidepressants

Withdrawal Syndromes Alcohol Antiepileptic drugs Baclofen Barbiturates Benzodiazepams

CNS Lesions Acute hydrocephalus Anoxic or hypoxic insult Arteriovenous malformations Brain metastases Cerebrovascular accident Chronic epilepsy Eclampsia Head trauma Intracerebral hemorrhage Neoplasm Neurosurgery Posterior reversible leukoencephalopathy Remote structural injury

The Seizing PatientCase I: First time seizure presenting to ER, seizure resolved by time off arrival

Was this truly a seizure?seizureAbrupt onsetBrief durationAltered mental statusPurposeless activityUnprovoked Post-ictal state Syncope classically masquerades as seizure and may include body movements1) Clues that episode may have been syncope: Brief episode of unconscousness followed by rapid return of mental staus2) Clues that episode may have been seizure:Bowel/bladder incontinence, presence of post-ictal confusional periodPerform thorough history and physical looking for clues to conditions that may lead to seizures:Review history for use of drugsReview history for neurological symptoms suggesting focal disease:Ask about any changes in mental status, motor or sensory functionPerform physical exam:Examine head and tongue for signs of traumaExamine for focal neuro deficits may point to speficic brain lesion as etiology of seizures:Focal motor or sensory deficits, ocular movement abnormalities, gait instability, pronator driftLab testing:Blood sugar, PT, urea and electrolytesECGCT brain EEG

Should Anti-Epileptics be started from the Emergency Department?

Case IIPatient with known H/O seizure presenting to ERSeizure resolved by time off arrival Drug level: If anti-epileptic dug can be measured and is at subtherapeutic levelsIf anti-epileptic drug can be measured and is at therapeutic levelsIf anti-epileptic drug cannot be measuredCase IIIParamedics call with status epilepticus notification 54 yrs old male found seizing at home, tonic clonic type pattern Negative PMHx and family HxRBS 100BP 180/100, HR 110/min, RR 20Paramedics have attempted multiple IV, all attempts failed Paramedics call for orders; what is your response?Case IIIStatus epilepticus: Pre-Hospital: no IV access:IM midazolam 0.2mg/kg to 10mg maxBuccal midazolam 0.2mg/kg to 10mg maxRectal diazepam 0.5 mg/kg to 20 mg max Status epilepticus: Pre-Hospital: IV access obtained :Lorazepam IV 0.1mg /kg to 4mg maxDiazepam IV 0.2mg /kg to 10 mg max

Case III, cont,Paramedics have given lorazepam 2mg IV Pt started seizing again as paramedics pull into EDWhat is next action:RSIFosphenytoin Lorazepam 2-4 mg iv Diazepam 5-10 mg iv Rapid assessment and stabilization A B C D Lorazepam Paediatric dose: 0.1mg/kg bolus Adults: 2-4mg bolus May repeat twice prn MidazolamHighly lipophilic drug:May be given intramuscularly or across mucous membranes with high resultant peak serum levelsFast onset of actionHeat stable and easily stored for EMS useDiazepamHighly lipophilic drugAvailable as gel with good efficacy when given via rectal routeHeat stable and easily stored for EMS useWill control seizures when given intravenouslyMay be less optimal than lorazepamLorazepamLess lipophilic properties-not optimal when given via intramuscular routeLonger redistribution half life over diazepam as less lipophilicHeat labile and should be refrigerated for long term storageIf given in adequate doses, will terminate seizures in 90% patientsAllow 5 minutes to assess for drug efficacyOnce 8-12 mg of lorazepam given and patient still seizing:Defines refractory status epilepticus and time to move to new drugCase III, cont,Pt continues to seize despite administration of 12 mg lorazepamWhat is next?

Phenytoin IVPhosphenytoin

Second line approachPhenytoin IVworks by stabilizing sodium channels20-30 mg/kg bolus Max rate 1mg/kg/min or 50 mg/minDisadvantages: Local tissue irritation/destruction if line infiltratesCannot be given IMmay cause metabolic acidosis / hypotensionCardiac arrhythmias may occur in rare cases-monitor on telemetry

PhosphenytoinDisodium phosphate ester of pheytoinMeasured in phosphenytoin units (PE)Freely soluble in aqueous solutionsLess tissue damage if accidentally extravasatesCan be given intramuscularly20-30 PE/kg bolusMax rate 3PE/kg/min or 150 PE/minDisadvantages:May rarely cause hypotension and arrhythmiasDrug hypersensitivity syndrome:Cross reactivity between phenytoin/phosphenytoin, phenobarbital, carbamezipine and primidone resulting in rash, fever, lympadenopathy and occasional liver/renal damageCase III, cont,Pt still seizing with tonic clonic movementPulse oximetry 96%What medications would you order now?Third line approachMany experts/pathways are now placing IV valproate and levetiracetam before use of phenobarbital.Third line approachValproate IVClassic anti-epileptic drug that also stabilizes sodium channelsIV form now available and has been found effective in refractory status epilepticus20 mg/kg bolus Max rate 5mg/kg/min or 300mg/minCan cause hepatotoxicity

Levetiracetam

Newer anti-epileptic drug that has multiple sites of action:Blocks calcium dependent neurotransmitter release and modulates GABA receptorsIV Formulation is now approved in adultsPediatric use not FDA approved20 mg/kg bolus Max rate 5mg/kg/min or 300mg/min

PhenobarbitalMultiple effects include GABA mediated neuronal depressionStill considered first line therapy in treating seizures in neonatesAdvantages include rescue therapy in refractory status epilepticus unresponsive to other medications20mg bolus Max rate 1-2mg /kg /min or 50-100 mg/minPrepare for intubationPhenobarbital can cause high rate of hypotensionIV fluids should be given simultaneouslyPressors may also be needed to maintain blood pressure

Propofol:

Used as constant infusionInitiate with 1-2 mg/kg bolusContinue infusion with 1 mg/kg/hourAssociated with high rate of hypotension:Give intravenous fluidsPressors may be neededMidazolam

Used as constant infusionInitiate with 0.2 mg/kg bolus to max of 10 mgContinue infusion with 0.2 mg/kg/hourSpecial scenarios1) Sympathomimetics:Classic is cocaineMaximize benzodiazepines dosagesPhenobarbital indicated instead of phenytoin for second line therapy2) Alcohol Withdrawal Seizures:Maximize benzodiazepine dosePhenobarbital indicated instead of phenytoin for second line therapy3) Other specific drugs that may cause seizures:Generally initiate therapy with benzodiazepinePhenobarbital generally indicated as second line agent over pheytoinCase IV28-yrs old female present to ED with h/o seizurePMHX NSVD 3 weeks agoHas second seizure in ED What is your order?PregnancySeizures may be sign of eclampsia after 20 weeks gestationMay occur post-partum in segment of affected patientsLoad with 4-6 grams magnesium sulfateContinue infusion with 1-2 grams per hourFebrile seizure in childrenSeizure occurring in the presence of fever without CNS infection or other cause Occurs in 2 to 5% of all children between the age of 6 months and 5 yearsSimple vs complex Uncomplicated seizure:Duration of less than 15 minutes in child 6 months to 5 yearsUsually tonic-clonic, without focalityRelated more to rate of rise in temperature, rather than absolute temperatureUsual care-no specific seizure workupPerform infection workup as indicated Complicated seizure:Duration greater than 15 minutesFocality to seizure presentationOccurring in children before age 6 months and after 5 yearsMay require specific seizure workup (CT, LP)ConclusionSeizure is a common disease in routine Emergency Medicine practiceNewer second generation medications increasingly usedSerum levels cannot be rapidly obtained in Emergency DepartmentNeurology input may be needed to modulate dosesConclusionStatus Epilepticus:Newer definition has shortened duration of seizure activity to 5 minutesAggressive therapy to rapidly break seizures crucialAs seizures become prolonged-more difficult to control (kindling theory)IV formulations of valproate and levetiracetam now availablePreliminary studies suggest role for these agents in refractory status epilepticus before intitating phenobarbital43ConclusionDrug Related Seizures (intoxications, withdrawal):Majority Toxicology concensus is to first maximize benzodiazepinesPhenobarbital generally preferred over phenytoin for second line therapy