1. Clinical Decisions in the Management of Seizures and Status Epilepticus in the Emergency Department Andy Jagoda, MD, FACEP Professor of Emergency Medicine Mount Sinai School of Medicine New York, New York

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

3. The patient is worked-up as an outpatient and diagnosed with a seizure disorder. She is treated with phenytoin, 300 mg qhs. She is brought to the ED by EMS status post a “typical” event but back to baseline. Her serum phenytoin level is <1 ug/ml. Which of the following is the best management plan? Fosphenytoin, 20 PE/kg, IM in the deltoid Fosphenytoin, 20 PE/kg, IM in the deltoid Fosphenytoin, 20 PE/kg, IV at 300 mg/min Fosphenytoin, 20 PE/kg, IV at 300 mg/min Phenytoin, 20 mg/kg IV at 150 mg/min Phenytoin, 20 mg/kg IV at 150 mg/min Phenytoin, 20 mg/kg po and discharge after 4 hrs Phenytoin, 20 mg/kg po and discharge after 4 hrs Lorazepam, 2 mg, IV and discharge after one hour Lorazepam, 2 mg, IV and discharge after one hour

4. While in the ED, she goes into status epilepticus. The seizures do not stop despite lorazepam, 10 mg, and phenytoin 20 mg/kg. Which of the following is not 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 / kg Phenobarbital, 20 mg / kg Pentobarbital, 3 mg / kg Pentobarbital, 3 mg / kg Propofol, 1 mg / kg Propofol, 1 mg / kg Vecuronium,.1 mg /kg Vecuronium,.1 mg /kg

5. INTRODUCTION 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

6. Seizures in Pregnancy Evaluation same as in the non –pregnant patientEvaluation same as in the non –pregnant patient Evaluation should focus on precipitating factors (sleep deprivation, AED noncompliance, stress)Evaluation should focus on precipitating factors (sleep deprivation, AED noncompliance, stress) Pregnancy changes AED free drug levelsPregnancy changes AED free drug levels Fetal monitoring must be includedFetal 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; 345:1455-1463 * Lancet 1995; 345:1455-1463

7. Seizures in Adults New onset sz highest incidence patients 60 yrsNew onset sz highest incidence patients 60 yrs 50% of szs in the elderly are related to stroke50% of szs in the elderly are related to stroke Tumors and drugs/alcoholTumors and drugs/alcohol NCSE presents as confusion or altered mental statusNCSE presents as confusion or altered mental status Etiology often unknown but may result from stroke, drug withdrawal or electrolyte abnormalitiesEtiology often unknown but may result from stroke, drug withdrawal or electrolyte abnormalities

8. New Onset Seizures 5% - 6% of the population will have at least one seizure during their lifetime5% - 6% of the population will have at least one seizure during their lifetime Diagnostic work-up in the ED depends on the clinical exam and co-morbiditiesDiagnostic work-up in the ED depends on the clinical exam and co-morbidities Etiologies of first time adult seizures are age group dependent and co-morbidity dependentEtiologies of first time adult seizures are age group dependent and co-morbidity dependent HIVHIV Chronic alcohol consumption (30-60 year olds)Chronic alcohol consumption (30-60 year olds) Cerebral vascular insults (>60 year old)Cerebral vascular insults (>60 year old)

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

10. What laboratory tests are indicated in the ED 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. Ann Emerg Med 1990; 19:373-377. Prospective. 136 patients) Nypaver. ED laboratory evaluation of hcildren with seizures: Dogma or dilemma? Ped Emerg Care 1992; 8:13-21. Retrospective 308 patients)

11. Lumbar 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 baselineHas returned to baseline Has no fever or meningeal signsHas no fever or meningeal signs There are no cases reportedof meningitis presenting as a simple tonic clonic seizureThere are no cases reportedof meningitis presenting as a simple tonic clonic seizure Postictal pleocytosis (>5 polys in the CSF) has been reported in 2 - 18% of patients who have had a GTCSPostictal pleocytosis (>5 polys in the CSF) has been reported in 2 - 18% of patients who have had a GTCS Pesola G,. New onset generalized seizures in patients with AIDS. Acad Emerg Med. 1998; 5:905-911. Retrospective review, 26 patients Green S,. Can seizures be the sole manifestation of meningitis in febrile children? Pediatrics 1993; 92:527-534. Retrospective. 503 cases

12. Neuroimaging: Head CT and MR Three per cent to 41% of patients with a first time seizure have an abnormal head CTThree per cent to 41% of patients with a first time seizure have an abnormal head CT Imaging is dependent on the urgency of the evaluation and patient stabilityImaging is dependent on the urgency of the evaluation and patient stability Literature interpretation depends on outcome measure usedLiterature interpretation depends on outcome measure used Tardy. AJEM. 1995; 13:1-5. Retrospective review. 247 patients. Henneman AEM 1994; 24:1108-1114. Retrospective. 294 patients).

13. Neuroimaging in New Onset Seizures ACEP, AAN, AANS, ASNR. Practice Parameter: ED neuroimaging in the seizure pt. Ann Emerg Med 1996; 27:114-118. Evidence based practice guidelineACEP, AAN, AANS, ASNR. Practice Parameter: ED neuroimaging in the seizure pt. Ann Emerg Med 1996; 27:114-118. Evidence based practice guideline Emergent CT for patients with altered mental status, trauma, focal exam, immunocompromise, fever, co- morbitidityEmergent CT for patients with altered mental status, trauma, focal exam, immunocompromise, fever, co- morbitidity Patients who are alert with a nonfocal exam can have an outpatient studyPatients who are alert with a nonfocal exam can have an outpatient study Focal abnormalities on CT are reported in up to 40% of patients with new onset seizures; up to 20% have non- focal examsFocal abnormalities on CT are reported in up to 40% of patients with new onset seizures; up to 20% have non- focal exams MRI is better than CT in detecting subtle lesions (e.g., hippocampal sclerosis) but impact on care is controversialMRI is better than CT in detecting subtle lesions (e.g., hippocampal sclerosis) but impact on care is controversial

14. 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 recurrence, ie, etiologyDecision to initiate AED treatment depends on the risk of recurrence, 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 oral or IV phenytoin; IM forphenytoin; IV valproic acidPatients needing immediate AED treatment can be loaded with oral or IV phenytoin; IM forphenytoin; IV valproic acid Decision to admit depends on assessed risk of recurrence, patient compliance, and patients social circumstancesDecision to admit depends on assessed risk of recurrence, patient compliance, and patients social circumstances

15. The patient is worked-up as an outpatient and diagnosed with a seizure disorder. She is treated with phenytoin, 300 mg qhs. She is brought to the ED by EMS status post a “typical” event but back to baseline. Her serum phenytoin level is <1 ug/ml. Which of the following is the best management plan? Fosphenytoin, 20 PE/kg, IM in the deltoid Fosphenytoin, 20 PE/kg, IM in the deltoid Fosphenytoin, 20 PE/kg, IV at 300 mg/min Fosphenytoin, 20 PE/kg, IV at 300 mg/min Phenytoin, 20 mg/kg IV at 150 mg/min Phenytoin, 20 mg/kg IV at 150 mg/min Phenytoin, 20 mg/kg po and discharge after 4 hrs Phenytoin, 20 mg/kg po and discharge after 4 hrs Lorazepam, 2 mg, IV and discharge after one hour Lorazepam, 2 mg, IV and discharge after one hour

16. AED Loading In patients who have seized and returned to baseline, no AED loading strategy has been shown to be superior in preventing seizure recurrenceIn patients who have seized and returned to baseline, no AED loading strategy has been shown to be superior in preventing seizure recurrence No outcome studies exist comparing loading strategiesNo outcome studies exist comparing loading strategies IV phenytoin achieves therapeutic serum levels by the end of the infusionIV phenytoin achieves therapeutic serum levels by the end of the infusion IM fosphenytoin achieves therapeutic serum levels within one hour post injectionIM fosphenytoin achieves therapeutic serum levels within one hour post injection PO phenytoin, 19 mg/kg in males and 25 mg/kg in females single dose achieves therapeutic serum levels in 4 hoursPO phenytoin, 19 mg/kg in males and 25 mg/kg in females single dose achieves therapeutic serum levels in 4 hours Ratanakorn. J Neuro Sci 1997; 147:89-92 Van der Meyden. Epilepsia 1994; 35:189-194

17. Valproic Acid Loading 15 mg / kg oral, rectal, or intravenous15 mg / kg oral, rectal, or intravenous Oral loading rapid absorption but limited by GI side effectsOral loading rapid absorption but limited by GI side effects IV loading recommended over one hourIV loading recommended over one hour Has been given faster at 200 mg / min in status epilepticus as a third line drug*Has been given faster at 200 mg / min in status epilepticus as a third line drug* Drug Invest 1993: 5:154-159

18. The patient is worked-up as an outpatient and diagnosed with a seizure disorder. She is treated with phenytoin, 300 mg qhs. She is brought to the ED by EMS status post a “typical” event but back to baseline. Her serum phenytoin level is <1 ug/ml. Which of the following is the best management plan? Fosphenytoin, 20 PE/kg, IM in the deltoid Fosphenytoin, 20 PE/kg, IM in the deltoid Fosphenytoin, 20 PE/kg, IV at 300 mg/min Fosphenytoin, 20 PE/kg, IV at 300 mg/min Phenytoin, 20 mg/kg IV at 150 mg/min Phenytoin, 20 mg/kg IV at 150 mg/min Phenytoin, 20 mg/kg po and discharge after 4 hrs Phenytoin, 20 mg/kg po and discharge after 4 hrs Lorazepam, 2 mg, IV and discharge after one hour Lorazepam, 2 mg, IV and discharge after one hour

19. While in the ED, she goes into status epilepticus. The seizures do not stop despite lorazepam, 10 mg, and phenytoin 20 mg/kg. Which of the following is not 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/hrPentobarbital, 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

20. Status 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 status22% 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

21. STATUS EPILEPTICUS: SE Working Group (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/minLorazepam.1 mg/kg at 2 mg/min If diazepam is used, phenytoin must be started simulatneouslyIf diazepam is used, phenytoin must be started simulatneously Phenytoin 20 mg/kg at 25-50 mg/min (fosphenytoin 20 PE/kg at 150 mg/min)Phenytoin 20 mg/kg at 25-50 mg/min (fosphenytoin 20 PE/kg at 150 mg/min) Repeat phenytoin 5 mg/kgRepeat phenytoin 5 mg/kg Phenobarbital 20 mg/kg at 100 mg/minPhenobarbital 20 mg/kg at 100 mg/min Valproic acid 20 mg/kgValproic acid 20 mg/kg Epilepsy Foundation of America. JAMA 1993;270:854-859

22. VA 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 seizures or mortality at 12 hours or 30 daysNo difference among the four groups in recurrance of seizures 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;339:792-798

23. Differential Diagnosis of a Prolonged Postictal State Intracranial catastropheIntracranial catastrophe HypoglycemiaHypoglycemia Drug effectDrug effect SCSESCSE NCSENCSE

24. Nonconvulsive Status Epilepticus NCSE vs SCSENCSE vs SCSE Prognosis worse with SCSEPrognosis worse with SCSE Clinical characteristicsClinical characteristics mild cognitive deficits to coma*mild cognitive deficits to coma* Incidence: 14% after CSE**Incidence: 14% after CSE** Diagnosis: Clinical and EEGDiagnosis: Clinical and EEG TreatmentTreatment * Tomson. Epilepsia 1992;33:829-835 ** DeLorenzo. Epilepsia 1998; 39:833-840

25. EEG in the Emergency Department A properly performed EEG is helpful in establishing etiology and directing therapyA properly performed EEG is helpful in establishing etiology and directing therapy A “normal” EEG Does not exclude an epileptic focusA “normal” EEG Does not exclude an epileptic focus EEG in the ED:EEG in the ED: Patients with altered MS suspected of NCSE or SCSEPatients with altered MS suspected of NCSE or SCSE Patients who are paralyzed or in pentobarbital comaPatients who are paralyzed or in pentobarbital coma “Seizing” patients suspected of being in psychogenic status epilepticus“Seizing” patients suspected of being in psychogenic status epilepticus

26. Refractory 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 mg/kg/hr infusion) found to be more effective but associated with higher incidence of hypotensionPentobarbital (13mg/kg load followed by 2 mg/kg/hr infusion) found to be more effective but associated with higher incidence of hypotension Claassen. Epilepsia 2002; 43:146-153.

27. While in the ED, she goes into status epilepticus. The seizures do not stop despite lorazepam, 10 mg, and phenytoin 20 mg/kg. Which of the following is not 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/hrPentobarbital, 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

28. Conclusions Management of a patient with a first time seizure is based on a careful neurologic exam, and the results of a chemistry panel, head CT, and EEGManagement of a patient with a first time seizure is based on a careful neurologic exam, and the results of a chemistry panel, head CT, and EEG Oral phenytoin loading provides “therapeutic” serum levels four hours post-load in most casesOral phenytoin loading provides “therapeutic” serum levels 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, midazolam, or propofol are third line agentsIn refractory status epilepticus, pentobarbital, midazolam, or propofol are third line agents