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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.
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Clinical Decisions in the Management of Seizures and Status Epilepticus in the Emergency Department Andy Jagoda, MD, FACEPProfessor of Emergency MedicineMount Sinai School of MedicineNew York, New York
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 test • Electrolytes • Glucose • CSF analysis • CT
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, IV at 300 mg/min • Phenytoin, 20 mg/kg IV at 150 mg/min • Phenytoin, 20 mg/kg po and discharge after 4 hrs • Lorazepam, 2 mg, IV and discharge after one hour
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) • Phenobarbital, 20 mg / kg • Pentobarbital, 3 mg / kg • Propofol, 1 mg / kg • Vecuronium, .1 mg /kg
INTRODUCTION • Classification • Focal vs Generalized • Motor vs Nonmotor • Etiologies: Key is to identify treatable causes • Vascular event (stroke, SAH, subdural) • Metabolic abnormality (hypoglycemia) • Infections • Toxicity (intentional, nonintentional) • Drug withdrawal • Tumor • Pregnancy
Seizures in Pregnancy • Evaluation same as in the non –pregnant patient • Evaluation should focus on precipitating factors (sleep deprivation, AED noncompliance, stress) • Pregnancy changes AED free drug levels • Fetal monitoring must be included • Assess for eclampsia • Mg SO4 therapy of choice in eclamptic szs * * Lancet 1995; 345:1455-1463
Seizures in Adults • New onset sz highest incidence patients < 1 yr and > 60 yrs • 50% of szs in the elderly are related to stroke • Tumors and drugs/alcohol • NCSE presents as confusion or altered mental status • Etiology often unknown but may result from stroke, drug withdrawal or electrolyte abnormalities
New Onset Seizures • 5% - 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-morbidities • Etiologies of first time adult seizures are age group dependent and co-morbidity dependent • HIV • Chronic alcohol consumption (30-60 year olds) • Cerebral vascular insults (>60 year old)
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 test • Electrolytes • Glucose • CSF analysis • CT
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)
Lumbar Puncture • A LP in the ED is not indicated if the patient: • Is not immunocompromised • Has returned to baseline • Has no fever or meningeal signs • There 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 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
Neuroimaging: Head CT and MR • Three 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 stability • Literature 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).
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 guideline • Emergent 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 study • Focal 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 controversial
Treatment of First Time Seizures • Coordinated care with neurologist / primary care provider • Decision to initiate AED treatment depends on the risk of recurrence, ie, etiology • Etiology, CT and EEG findings are the strongest predictors • Recurrence risk is up to 20% within the first 24 hours • 23% to 71% within 2 years • Patients 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 circumstances
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, IV at 300 mg/min • Phenytoin, 20 mg/kg IV at 150 mg/min • Phenytoin, 20 mg/kg po and discharge after 4 hrs • Lorazepam, 2 mg, IV and discharge after one hour
AED Loading • In 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 strategies • IV phenytoin achieves therapeutic serum levels by the end of the infusion • IM 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 hours Ratanakorn. J Neuro Sci 1997; 147:89-92 Van der Meyden. Epilepsia 1994; 35:189-194
Valproic Acid Loading • 15 mg / kg oral, rectal, or intravenous • Oral loading rapid absorption but limited by GI side effects • IV loading recommended over one hour • Has been given faster at 200 mg / min in status epilepticus as a third line drug* Drug Invest 1993: 5:154-159
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, IV at 300 mg/min • Phenytoin, 20 mg/kg IV at 150 mg/min • Phenytoin, 20 mg/kg po and discharge after 4 hrs • Lorazepam, 2 mg, IV and discharge after one hour
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/hr • Phenobarbital, 20 mg / kg • Pentobarbital, 5-15 mg / kg; 2 mg/kg/hr • Propofol, 1 mg / kg; 4 mg/kg/hr • Vecuronium, .1 mg /kg
Status Epilepticus • 126,000 - 195,000 cases in the US / year • 25% of cases are NCSE or SGCSE • 22% mortality in convulsive status • 26% in adults, 3% in children • Undetermined in NCSE or SGCSE • M & M associated with: • Underlying etiology • Co-morbidity • Duration of event
STATUS EPILEPTICUS: SE Working Group(Consensus Document) • Management must simultaneously address: • Stabilization: ABCs • Diagnostic testing including (including rapid glucose) • Pharmacologic interventions • Drug therapy • Lorazepam .1 mg/kg at 2 mg/min • If 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) • Repeat phenytoin 5 mg/kg • Phenobarbital 20 mg/kg at 100 mg/min • Valproic acid 20 mg/kg Epilepsy Foundation of America. JAMA 1993;270:854-859
VA Cooperative Study • Prospective study: 384 patients in CSE • Four treatment regimens • Phenytoin 18 mg/kg • Diazepam plus phenytoin • Phenobarbital 15 mg/kg • Lorazepam .1 mg/kg • No difference among the four groups in recurrance of seizures or mortality at 12 hours or 30 days • Trend in favor of lorazepam; easiest to use NEJM 1998;339:792-798
Differential Diagnosis of a Prolonged Postictal State • Intracranial catastrophe • Hypoglycemia • Drug effect • SCSE • NCSE
Nonconvulsive Status Epilepticus • NCSE vs SCSE • Prognosis worse with SCSE • Clinical characteristics • mild cognitive deficits to coma* • Incidence: 14% after CSE** • Diagnosis: Clinical and EEG • Treatment * Tomson. Epilepsia 1992;33:829-835 ** DeLorenzo. Epilepsia 1998; 39:833-840
EEG in the Emergency Department • A properly performed EEG is helpful in establishing etiology and directing therapy • A “normal” EEG Does not exclude an epileptic focus • EEG in the ED: • Patients with altered MS suspected of NCSE or SCSE • Patients who are paralyzed or in pentobarbital coma • “Seizing” patients suspected of being in psychogenic status epilepticus
Refractory Status Epilepticus • Systematic review of the literature • 28 studies; 193 patients • 48% mortality • Compared propofol, midazolam, and pentobarbital • Outcome: 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 hypotension Claassen. Epilepsia 2002; 43:146-153.
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/hr • Phenobarbital, 20 mg / kg • Pentobarbital, 5-15 mg / kg; 2 mg/kg/hr • Propofol, 1 mg / kg; 4 mg/kg/hr • Vecuronium, .1 mg /kg
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 EEG • Oral phenytoin loading provides “therapeutic” serum levels four hours post-load in most cases • Lorazepam is the best first line treatment for seizures • In refractory status epilepticus, pentobarbital, midazolam, or propofol are third line agents