Clinical Decisions in the Management of Clinical Decisions in the Management of Seizures and Status Epilepticus in the Seizures and Status Epilepticus in the

Emergency Department Emergency Department

Andy Jagoda, MD, FACEPAndy Jagoda, MD, FACEPProfessor of Emergency MedicineProfessor of Emergency MedicineMount Sinai School of MedicineMount Sinai School of Medicine

New York, New YorkNew York, New York

A 20 year old female with no known medical problems A 20 year old female with no known medical problems has a generalized tonic clonic seizure that lasts 2 minutes. has a generalized tonic clonic seizure that lasts 2 minutes. After a short postictal period, she returns to her baseline, After a short postictal period, she returns to her baseline, feels well, has a normal physical and neurologic exam. feels well, has a normal physical and neurologic exam. Which of the following laboratory tests is not indicated in Which of the following laboratory tests is not indicated in the ED?the ED?

• Pregnancy testPregnancy test• ElectrolytesElectrolytes• GlucoseGlucose• CSF analysisCSF analysis• CT CT

The patient is worked-up as an outpatient and diagnosed The patient is worked-up as an outpatient and diagnosed with a seizure disorder. She is treated with phenytoin, with a seizure disorder. She is treated with phenytoin, 300 mg qhs. She is brought to the ED by EMS status post 300 mg qhs. She is brought to the ED by EMS status post a “typical” event but back to baseline. Her serum a “typical” event but back to baseline. Her serum phenytoin level is <1 ug/ml. Which of the following is phenytoin level is <1 ug/ml. Which of the following is the best management plan? the best management plan?

• Fosphenytoin, 20 PE/kg, IM in the deltoidFosphenytoin, 20 PE/kg, IM in the deltoid• Fosphenytoin, 20 PE/kg, IV at 300 mg/minFosphenytoin, 20 PE/kg, IV at 300 mg/min• Phenytoin, 20 mg/kg IV at 150 mg/minPhenytoin, 20 mg/kg IV at 150 mg/min• Phenytoin, 20 mg/kg po and discharge after 4 hrsPhenytoin, 20 mg/kg po and discharge after 4 hrs• Lorazepam, 2 mg, IV and discharge after one hourLorazepam, 2 mg, IV and discharge after one hour

While in the ED, she goes into status epilepticus. While in the ED, she goes into status epilepticus. The seizures do not stop despite lorazepam, 10 The seizures do not stop despite lorazepam, 10 mg, and phenytoin 20 mg/kg. Which of the mg, and phenytoin 20 mg/kg. Which of the following is following is notnot a reasonable third line therapy? a reasonable third line therapy?

• A second half load of phenytoin (10 mg /kg)A second half load of phenytoin (10 mg /kg)

• Phenobarbital, 20 mg / kgPhenobarbital, 20 mg / kg

• Pentobarbital, 3 mg / kgPentobarbital, 3 mg / kg

• Propofol, 1 mg / kgPropofol, 1 mg / kg

• Vecuronium, .1 mg /kgVecuronium, .1 mg /kg

INTRODUCTIONINTRODUCTION

• ClassificationClassification• Focal vs GeneralizedFocal vs Generalized• Motor vs NonmotorMotor vs Nonmotor

• Etiologies: Key is to identify treatable causesEtiologies: Key is to identify treatable causes• Vascular event (stroke, SAH, subdural)Vascular event (stroke, SAH, subdural)• Metabolic abnormality (hypoglycemia)Metabolic abnormality (hypoglycemia)• InfectionsInfections• Toxicity (intentional, nonintentional)Toxicity (intentional, nonintentional)• Drug withdrawalDrug withdrawal• TumorTumor• PregnancyPregnancy

Seizures in PregnancySeizures in Pregnancy

• Evaluation same as in the non –pregnant patientEvaluation same as in the non –pregnant patient• Evaluation should focus on precipitating factors Evaluation should focus on precipitating factors

(sleep deprivation, AED noncompliance, stress)(sleep deprivation, AED noncompliance, stress)• Pregnancy changes AED free drug levels Pregnancy changes AED free drug levels • Fetal monitoring must be included Fetal monitoring must be included • Assess for eclampsiaAssess for eclampsia• Mg SO4 therapy of choice in eclamptic szs Mg SO4 therapy of choice in eclamptic szs **

* Lancet 1995; 345:1455-1463Lancet 1995; 345:1455-1463

Seizures in AdultsSeizures in Adults

• New onset sz highest incidence patients < 1 New onset sz highest incidence patients < 1 yr and > 60 yrsyr and > 60 yrs

• 50% of szs in the elderly are related to stroke50% of szs in the elderly are related to stroke• Tumors and drugs/alcohol Tumors and drugs/alcohol

• NCSE presents as confusion or altered mental NCSE presents as confusion or altered mental status status • Etiology often unknown but may result Etiology often unknown but may result

from stroke, drug withdrawal or electrolyte from stroke, drug withdrawal or electrolyte abnormalitiesabnormalities

New Onset SeizuresNew Onset Seizures

• 5% - 6% of the population will have at least one 5% - 6% of the population will have at least one seizure during their lifetimeseizure during their lifetime

• Diagnostic work-up in the ED depends on the Diagnostic work-up in the ED depends on the clinical exam and co-morbiditiesclinical exam and co-morbidities

• Etiologies of first time adult seizures are age Etiologies of first time adult seizures are age group dependent and co-morbidity dependent group dependent and co-morbidity dependent • HIVHIV• Chronic alcohol consumption (30-60 year Chronic alcohol consumption (30-60 year

olds)olds)• Cerebral vascular insults (>60 year old)Cerebral vascular insults (>60 year old)

A 20 year old female with no known medical problems A 20 year old female with no known medical problems has a generalized tonic clonic seizure that lasts 2 minutes. has a generalized tonic clonic seizure that lasts 2 minutes. After a short postictal period, she returns to her baseline, After a short postictal period, she returns to her baseline, feels well, has a normal physical and neurologic exam. feels well, has a normal physical and neurologic exam. Which of the following laboratory tests is not indicated in Which of the following laboratory tests is not indicated in the ED?the ED?

• Pregnancy testPregnancy test• ElectrolytesElectrolytes• GlucoseGlucose• CSF analysisCSF analysis• CT CT

What laboratory tests are indicated in the ED What laboratory tests are indicated in the ED evaluation of a patient with a new onset sz?evaluation of a patient with a new onset sz?

• ACEP Clinical Policy. Ann Emerg Med 1997; 29:706

• Patients with a normal exam and no co-morbities: Glucose level, electrolytes, and pregnancy test

• Consider a drug of abuse screen

• Patients with co-morbidities require more extensive testing

• CPK and prolactin levels are of limited value in the ED

Turnbull. Utility of laboratory studies in the ED in patients with a new onset sz. Turnbull. Utility of laboratory studies in the ED in patients with a new onset sz. Ann Emerg Med 1990; 19:373-377. Prospective. 136 patients)Ann Emerg Med 1990; 19:373-377. Prospective. 136 patients)

Nypaver. ED laboratory evaluation of hcildren with seizures: Dogma or Nypaver. ED laboratory evaluation of hcildren with seizures: Dogma or dilemma? Ped Emerg Care 1992; 8:13-21. Retrospective 308 patients) dilemma? Ped Emerg Care 1992; 8:13-21. Retrospective 308 patients)

Lumbar PunctureLumbar Puncture

• A LP in the ED is not indicated if the patient:A LP in the ED is not indicated if the patient:• Is not immunocompromisedIs not immunocompromised• Has returned to baseline Has returned to baseline • Has no fever or meningeal signsHas no fever or meningeal signs

• There are no cases reportedof meningitis presenting as There are no cases reportedof meningitis presenting as a simple tonic clonic seizurea simple tonic clonic seizure

• Postictal pleocytosis (>5 polys in the CSF) has been Postictal pleocytosis (>5 polys in the CSF) has been reported in 2 - 18% of patients who have had a GTCS reported in 2 - 18% of patients who have had a GTCS

Pesola G,. New onset generalized seizures in patients with AIDS.Pesola G,. New onset generalized seizures in patients with AIDS.Acad Emerg Med. 1998; 5:905-911. Retrospective review, 26 patientsAcad Emerg Med. 1998; 5:905-911. Retrospective review, 26 patients

Green S,. Can seizures be the sole manifestation of meningitis in febrile children? Green S,. Can seizures be the sole manifestation of meningitis in febrile children? Pediatrics 1993; 92:527-534. Retrospective. 503 casesPediatrics 1993; 92:527-534. Retrospective. 503 cases

Neuroimaging: Head CT and MRNeuroimaging: Head CT and MR

• Three per cent to 41% of patients with a first Three per cent to 41% of patients with a first time seizure have an abnormal head CTtime seizure have an abnormal head CT

• Imaging is dependent on the urgency of the Imaging is dependent on the urgency of the evaluation and patient stabilityevaluation and patient stability

• Literature interpretation depends on outcome Literature interpretation depends on outcome measure usedmeasure used

Tardy. AJEM. 1995; 13:1-5. Retrospective review. 247 patients. Tardy. AJEM. 1995; 13:1-5. Retrospective review. 247 patients.

Henneman AEM 1994; 24:1108-1114. Retrospective. 294 patients). Henneman AEM 1994; 24:1108-1114. Retrospective. 294 patients).

Neuroimaging in New Onset SeizuresNeuroimaging in New Onset Seizures

• ACEP, AAN, AANS, ASNR. Practice Parameter: ED ACEP, AAN, AANS, ASNR. Practice Parameter: ED neuroimaging in the seizure pt. Ann Emerg Med 1996; neuroimaging in the seizure pt. Ann Emerg Med 1996; 27:114-118. Evidence based practice guideline27:114-118. Evidence based practice guideline• Emergent CT for patients with altered mental status, Emergent CT for patients with altered mental status,

trauma, focal exam, immunocompromise, fever, co-trauma, focal exam, immunocompromise, fever, co-morbitiditymorbitidity

• Patients who are alert with a nonfocal exam can have Patients who are alert with a nonfocal exam can have an outpatient studyan outpatient study

• Focal abnormalities on CT are reported in up to 40% of Focal abnormalities on CT are reported in up to 40% of patients with new onset seizures; up to 20% have non-patients with new onset seizures; up to 20% have non-focal examsfocal exams

• MRI is better than CT in detecting subtle lesions (e.g., MRI is better than CT in detecting subtle lesions (e.g., hippocampal sclerosis) but impact on care is controversialhippocampal sclerosis) but impact on care is controversial

Treatment of First Time Seizures Treatment of First Time Seizures

• Coordinated care with neurologist / primary care providerCoordinated care with neurologist / primary care provider• Decision to initiate AED treatment depends on the risk of Decision to initiate AED treatment depends on the risk of

recurrence, ie, etiologyrecurrence, ie, etiology• Etiology, CT and EEG findings are the strongest predictorsEtiology, CT and EEG findings are the strongest predictors• Recurrence risk is up to 20% within the first 24 hoursRecurrence risk is up to 20% within the first 24 hours

• 23% to 71% within 2 years23% to 71% within 2 years• Patients needing immediate AED treatment can be loaded with Patients needing immediate AED treatment can be loaded with

oral or IV phenytoin; IM forphenytoin; IV valproic acid oral or IV phenytoin; IM forphenytoin; IV valproic acid • Decision to admit depends on assessed risk of recurrence, Decision to admit depends on assessed risk of recurrence,

patient compliance, and patients social circumstancespatient compliance, and patients social circumstances

The patient is worked-up as an outpatient and diagnosed The patient is worked-up as an outpatient and diagnosed with a seizure disorder. She is treated with phenytoin, with a seizure disorder. She is treated with phenytoin, 300 mg qhs. She is brought to the ED by EMS status post 300 mg qhs. She is brought to the ED by EMS status post a “typical” event but back to baseline. Her serum a “typical” event but back to baseline. Her serum phenytoin level is <1 ug/ml. Which of the following is phenytoin level is <1 ug/ml. Which of the following is the best management plan? the best management plan?

• Fosphenytoin, 20 PE/kg, IM in the deltoidFosphenytoin, 20 PE/kg, IM in the deltoid• Fosphenytoin, 20 PE/kg, IV at 300 mg/minFosphenytoin, 20 PE/kg, IV at 300 mg/min• Phenytoin, 20 mg/kg IV at 150 mg/minPhenytoin, 20 mg/kg IV at 150 mg/min• Phenytoin, 20 mg/kg po and discharge after 4 hrsPhenytoin, 20 mg/kg po and discharge after 4 hrs• Lorazepam, 2 mg, IV and discharge after one hourLorazepam, 2 mg, IV and discharge after one hour

AED LoadingAED Loading

• In patients who have seized and returned to baseline, no In patients who have seized and returned to baseline, no AED loading strategy has been shown to be superior in AED loading strategy has been shown to be superior in preventing seizure recurrencepreventing seizure recurrence

• No outcome studies exist comparing loading strategiesNo outcome studies exist comparing loading strategies

• IV phenytoin achieves therapeutic serum levels by the end IV phenytoin achieves therapeutic serum levels by the end of the infusionof the infusion

• IM fosphenytoin achieves therapeutic serum levels within IM fosphenytoin achieves therapeutic serum levels within one hour post injection one hour post injection

• PO phenytoin, 19 mg/kg in males and 25 mg/kg in females PO phenytoin, 19 mg/kg in males and 25 mg/kg in females single dose achieves therapeutic serum levels in 4 hourssingle dose achieves therapeutic serum levels in 4 hours

Ratanakorn. J Neuro Sci 1997; 147:89-92Van der Meyden. Epilepsia 1994; 35:189-194

Valproic Acid LoadingValproic Acid Loading

• 15 mg / kg oral, rectal, or intravenous15 mg / kg oral, rectal, or intravenous• Oral loading rapid absorption but limited Oral loading rapid absorption but limited

by GI side effectsby GI side effects• IV loading recommended over one hourIV loading recommended over one hour

• Has been given faster at 200 mg / min in Has been given faster at 200 mg / min in status epilepticus as a third line drug*status epilepticus as a third line drug*

Drug Invest 1993: 5:154-159Drug Invest 1993: 5:154-159

The patient is worked-up as an outpatient and diagnosed The patient is worked-up as an outpatient and diagnosed with a seizure disorder. She is treated with phenytoin, with a seizure disorder. She is treated with phenytoin, 300 mg qhs. She is brought to the ED by EMS status post 300 mg qhs. She is brought to the ED by EMS status post a “typical” event but back to baseline. Her serum a “typical” event but back to baseline. Her serum phenytoin level is <1 ug/ml. Which of the following is phenytoin level is <1 ug/ml. Which of the following is the best management plan? the best management plan?

• Fosphenytoin, 20 PE/kg, IM in the deltoidFosphenytoin, 20 PE/kg, IM in the deltoid• Fosphenytoin, 20 PE/kg, IV at 300 mg/minFosphenytoin, 20 PE/kg, IV at 300 mg/min• Phenytoin, 20 mg/kg IV at 150 mg/minPhenytoin, 20 mg/kg IV at 150 mg/min• Phenytoin, 20 mg/kg po and discharge after 4 hrsPhenytoin, 20 mg/kg po and discharge after 4 hrs• Lorazepam, 2 mg, IV and discharge after one hourLorazepam, 2 mg, IV and discharge after one hour

While in the ED, she goes into status epilepticus. While in the ED, she goes into status epilepticus. The seizures do not stop despite lorazepam, 10 The seizures do not stop despite lorazepam, 10 mg, and phenytoin 20 mg/kg. Which of the mg, and phenytoin 20 mg/kg. Which of the following is following is notnot a reasonable third line therapy? a reasonable third line therapy?

• Midazolam, .2 mg/kg; .1 mg/kg/hrMidazolam, .2 mg/kg; .1 mg/kg/hr

• Phenobarbital, 20 mg / kgPhenobarbital, 20 mg / kg

• Pentobarbital, 5-15 mg / kg; 2 mg/kg/hr Pentobarbital, 5-15 mg / kg; 2 mg/kg/hr

• Propofol, 1 mg / kg; 4 mg/kg/hrPropofol, 1 mg / kg; 4 mg/kg/hr

• Vecuronium, .1 mg /kgVecuronium, .1 mg /kg

Status EpilepticusStatus Epilepticus

• 126,000 - 195,000 cases in the US / year126,000 - 195,000 cases in the US / year

• 25% of cases are NCSE or SGCSE25% of cases are NCSE or SGCSE

• 22% mortality in convulsive status 22% mortality in convulsive status

• 26% in adults, 3% in children26% in adults, 3% in children

• Undetermined in NCSE or SGCSEUndetermined in NCSE or SGCSE

• M & M associated with:M & M associated with:

• Underlying etiologyUnderlying etiology

• Co-morbidityCo-morbidity

• Duration of eventDuration of event

STATUS EPILEPTICUS: SE Working GroupSTATUS EPILEPTICUS: SE Working Group(Consensus Document)(Consensus Document)

• Management must simultaneously address:Management must simultaneously address:• Stabilization: ABCsStabilization: ABCs• Diagnostic testing including (including rapid glucose)Diagnostic testing including (including rapid glucose)• Pharmacologic interventionsPharmacologic interventions

• Drug therapyDrug therapy• Lorazepam .1 mg/kg at 2 mg/min Lorazepam .1 mg/kg at 2 mg/min

• If diazepam is used, phenytoin must be started If diazepam is used, phenytoin must be started simulatneouslysimulatneously

• Phenytoin 20 mg/kg at 25-50 mg/min (fosphenytoin 20 PE/kg Phenytoin 20 mg/kg at 25-50 mg/min (fosphenytoin 20 PE/kg at 150 mg/min)at 150 mg/min)

• Repeat phenytoin 5 mg/kg Repeat phenytoin 5 mg/kg • Phenobarbital 20 mg/kg at 100 mg/min Phenobarbital 20 mg/kg at 100 mg/min • Valproic acid 20 mg/kg Valproic acid 20 mg/kg

Epilepsy Foundation of America. JAMA 1993;270:854-859

VA Cooperative StudyVA Cooperative Study

• Prospective study: 384 patients in CSEProspective study: 384 patients in CSE

• Four treatment regimensFour treatment regimens

• Phenytoin 18 mg/kgPhenytoin 18 mg/kg

• Diazepam plus phenytoinDiazepam plus phenytoin

• Phenobarbital 15 mg/kgPhenobarbital 15 mg/kg

• Lorazepam .1 mg/kgLorazepam .1 mg/kg

• No difference among the four groups in recurrance of No difference among the four groups in recurrance of seizures or mortality at 12 hours or 30 daysseizures or mortality at 12 hours or 30 days

• Trend in favor of lorazepam; easiest to useTrend in favor of lorazepam; easiest to use

NEJM 1998;339:792-798NEJM 1998;339:792-798

Differential Diagnosis of a Prolonged Postictal StateDifferential Diagnosis of a Prolonged Postictal State

• Intracranial catastropheIntracranial catastrophe

• HypoglycemiaHypoglycemia

• Drug effectDrug effect

• SCSESCSE

• NCSENCSE

Nonconvulsive Status EpilepticusNonconvulsive Status Epilepticus

• NCSE vs SCSENCSE vs SCSE• Prognosis worse with SCSEPrognosis worse with SCSE

• Clinical characteristicsClinical characteristics• mild cognitive deficits to comamild cognitive deficits to coma**

• Incidence: 14% after CSEIncidence: 14% after CSE****• Diagnosis: Clinical and EEGDiagnosis: Clinical and EEG• TreatmentTreatment

* * Tomson. Epilepsia 1992;33:829-835Tomson. Epilepsia 1992;33:829-835** DeLorenzo. Epilepsia 1998; 39:833-840** DeLorenzo. Epilepsia 1998; 39:833-840

EEG in the Emergency Department EEG in the Emergency Department

• A properly performed EEG is helpful in A properly performed EEG is helpful in establishing etiology and directing therapyestablishing etiology and directing therapy

• A “normal” EEG Does not exclude an epileptic A “normal” EEG Does not exclude an epileptic focusfocus

• EEG in the ED:EEG in the ED:• Patients with altered MS suspected of NCSE Patients with altered MS suspected of NCSE

or SCSEor SCSE• Patients who are paralyzed or in Patients who are paralyzed or in

pentobarbital comapentobarbital coma• ““Seizing” patients suspected of being in Seizing” patients suspected of being in

psychogenic status epilepticuspsychogenic status epilepticus

Refractory Status EpilepticusRefractory Status Epilepticus

• Systematic review of the literatureSystematic review of the literature• 28 studies; 193 patients28 studies; 193 patients• 48% mortality48% mortality

• Compared propofol, midazolam, and pentobarbitalCompared propofol, midazolam, and pentobarbital• Outcome: EEG burst suppressionOutcome: EEG burst suppression

• Pentobarbital (13mg/kg load followed by 2 Pentobarbital (13mg/kg load followed by 2 mg/kg/hr infusion) found to be more effective but mg/kg/hr infusion) found to be more effective but associated with higher incidence of hypotensionassociated with higher incidence of hypotension

Claassen. Epilepsia 2002; 43:146-153.

While in the ED, she goes into status epilepticus. While in the ED, she goes into status epilepticus. The seizures do not stop despite lorazepam, 10 The seizures do not stop despite lorazepam, 10 mg, and phenytoin 20 mg/kg. Which of the mg, and phenytoin 20 mg/kg. Which of the following is following is notnot a reasonable third line therapy? a reasonable third line therapy?

• Midazolam, .2 mg/kg; .1 mg/kg/hrMidazolam, .2 mg/kg; .1 mg/kg/hr

• Phenobarbital, 20 mg / kgPhenobarbital, 20 mg / kg

• Pentobarbital, 5-15 mg / kg; 2 mg/kg/hr Pentobarbital, 5-15 mg / kg; 2 mg/kg/hr

• Propofol, 1 mg / kg; 4 mg/kg/hrPropofol, 1 mg / kg; 4 mg/kg/hr

• Vecuronium, .1 mg /kgVecuronium, .1 mg /kg

ConclusionsConclusions

• Management of a patient with a first time seizure is Management of a patient with a first time seizure is based on a careful neurologic exam, and the results of based on a careful neurologic exam, and the results of a chemistry panel, head CT, and EEGa chemistry panel, head CT, and EEG

• Oral phenytoin loading provides “therapeutic” serum Oral phenytoin loading provides “therapeutic” serum levels four hours post-load in most caseslevels four hours post-load in most cases

• Lorazepam is the best first line treatment for seizuresLorazepam is the best first line treatment for seizures

• In refractory status epilepticus, pentobarbital, In refractory status epilepticus, pentobarbital, midazolam, or propofol are third line agents midazolam, or propofol are third line agents