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Clinical Decisions in Seizure Management Andy Jagoda, MD, FACEP Professor of Emergency Medicine Mount Sinai School of Medicine New York, New York. Objectives. Introduce the process of how clinical policies / practice guidelines are developed

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Clinical Decisions in Seizure Management Andy Jagoda, MD, FACEPProfessor of Emergency MedicineMount Sinai School of MedicineNew York, New York

objectives
Objectives
  • Introduce the process of how clinical policies / practice guidelines are developed
  • Provide an overview of seizures from the prospective of emergency medicine practice
  • Present the recommendations from the upcoming ACEP clinical policy on seizure management
seizure clinical policy
Seizure Clinical Policy
  • Frequently seen in the ED
  • Symptom of potentially life threatening disease
  • Associated with potential morbidity and mortality
  • ACEP Seizure Clinical Policy
    • 1993 - Approach based
    • 1997 - Revision
    • 2003 – Critical questions; evidence based
seizure epidemiology in emergency medicine
Seizure Epidemiology in Emergency Medicine
  • 1% of adult ED visits
  • 2% of pediatric ED visits
  • Most common ED etiologies are not epilepsy related:
    • Alcoholism
    • Stroke
    • Trauma
    • CNS infection
    • Metabolic / Toxin
    • Tumor
    • Fever in children
  • 50,000 – 100,000 ED cases of status epilepticus annually
    • 20% mortality
population based study of the epidemiology of status epilepticus
Population based study of the epidemiology of status epilepticus
  • Most epidemiology studies focus on patients with epilepsy and not on the epidemiology of seizures per se
  • Fewer than half the cases of status identified were managed by a neurologist
  • Over 50% of status cases occurred in patients with no prior history of epilepsy

Delorenzo et al. Neurology 1996; 46:1029-1035

seizure practice guidelines
Seizure Practice Guidelines
  • Treatment of convulsive status epilepticus. Epilepsy Foundation of America. JAMA 1993; 270:854-859.
  • The neurodiagnostic evaluation of the child with first simple febrile seizure. AAP. Pediatrics 1996; 97:769-775.
  • The role of phenytoin in the management of alcohol withdrawal syndrome. Am Soc Addiction Med 1994 / 1998
  • Evaluating the first nonfebrile seizure in chilren. AAN. Neurology 2000; 55:616-623.
  • Role of antiseizure prophylaxis following head injury. BTF / AANS. J Neurotrauma 2000; 17:549-553.
  • Treatment of the child with a first unprovoked seizure. AAN. Neurology 2003; 60:166-175
  • Antiepileptic drug prophylaxis in severe traumatic brain injury. Neurology 2003; 60:10-16
acep clinical policy
ACEP Clinical Policy
  • Identify questions of clinical importance to emergency department management of patients with seizures
  • Analyze the quality of data available related to acute management of patients with seizures
  • Differentiate anectodal experience from practice supported by evidence
acep clinical policy1
ACEP Clinical Policy
  • What lab tests are indicated in the otherwise healthy adult patient with a new onset seizure who has returned to a baseline normal neuro status?
  • Which new onset seizure patients who have returned to a normal baseline require neuroimaging in the ED?
  • Which new onset seizure patients who have returned to normal baseline need to be admitted to the hospital and / or started on an AED?
  • What are effective phenytoin dosing strategies for preventing sz recurrence in patients who present to the ED with a subtherapeutic serum phenytoin level?
  • What agent(s) should be administered to a patient in status who continues to seize despite a loading dose of a benzodiazepine and a phenytoin?
  • When should an EEG be performed in the ED?
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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
slide10

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
slide11

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
what laboratory tests are indicated in the ed evaluation of a patient with a new onset sz
What laboratory tests are indicated in the ED evaluation of a patient with a new onset sz?
  • Studies limited by heterogenous populations
  • No Class I studies
    • Prospective studies limited by design flaws
  • 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
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 reported of 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

slide14

What lab tests are indicated in the otherwise healthy adult patient with a new onset seizure who has returned to a baseline normal neuro status?(outcome measure is abnormal test that changes management)

  • Level A recommendations: None
  • Level B recommendations:
    • Determine a serum glucose and sodium on patients with a first time seizure with no co-morbidities who have returned to their baseline
    • Obtain a pregnancy test in women of child bearing age
    • Perform a LP after a head CT either in the ED or after admission on patients who are immunocompromised
neuroimaging head ct and mr
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
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
slide17
Which new onset seizure patients who have returned to a normal baseline require neuroimaging in the ED?(outcome measure: abnormal CT)
  • Level A recommendations: None
  • Level B recommendations:
    • When feasible, perform a head CT of the brain in the ED on patients with a first time seizure
    • Deferred outpatient neuroimaging may be utilized when reliable follow-up is available
treatment of first time seizures
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
slide19

Which new onset seizure patients who have returned to normal baseline need to be admitted to the hospital and / or started on an AED? (outcome measure: short term morbidity or mortality)

  • Level A recommendations: None
  • Level B recommendations: None
  • Level C recommenations:
    • Patients with a normal neurologic examination can be discharged from the ED with outpatient follow-up
    • Patients with a normal neurologic examination and no co-morbidities and no know structural brain disease do not need to be started on an anti-epileptic drug in the ED
aed loading
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

slide24

What are effective phenytoin dosing strategies for preventing sz recurrence in patients who present to the ED with a subtherapeutic serum phenytoin level? (outcome measure: short term seizure recurrence)

  • Level A recommendations. None specified.
  • Level B recommendations. None specified.
  • Level C recommendations:
    • Administer an intravenous or oral loading dose of phenytoin or intravenous or intramuscular fosphenytoin, and restart daily oral maintenance dosing.
slide25

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
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
nonconvulsive status epilepticus
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

status epilepticus se working group consensus document
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 mg/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
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

refractory 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.

slide31

What agent(s) should be administered to a patient in status who continues to seize despite a loading dose of a benzodiazepine and a phenytoin? (outcome measure: cessation of motor activity)

  • Level A recommendations. None specified.
  • Level B recommendations. None specified.
  • Level C recommendations:
    • Administer 1 of the following agents intravenously: “high-dose phenytoin,” phenobarbital, valproic acid, midazolam infusion, pentobarbital infusion, or propofol infusion.
differential diagnosis of prolonged postictal state
DIFFERENTIAL DIAGNOSIS OF PROLONGED POSTICTAL STATE
  • Intracranial catastrophe
  • Hypoglycemia
  • Drug effect
  • SCSE
  • NCSE
when should an eeg be performed in the ed
When should an EEG be performed in the ED?
  • Level A recommendations. None specified.
  • Level B recommendations. None specified.
  • Level C recommendations:
    • Consider an emergent EEG in patients suspected of being in nonconvulsive status epilepticus or in subtle convulsive status epilepticus, patients who have received a long-acting paralytic, or patients who are in a drug-induced coma.
summary
Summary
  • Evidence based clinical policies are useful tools in clinical decision making
  • Clinical policies do not create a “standard of care” but do provide a foundation for clinical practice at a national level
  • The current literature on acute seizure management does not support the creation of any “level A” recommendations
    • Only 2 of the 6 clinical questions have sufficient evidence to support “level B” recommendations
    • 4 of the 6 recommendations are “level C”
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