Clinical Decisions in Seizure Management Andy Jagoda, MD, FACEP Professor of Emergency Medicine Mount Sinai School of Medicine New York, New York

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

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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

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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

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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 461029-1035
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Seizure Practice Guidelines

• Treatment of convulsive status epilepticus.
  Epilepsy Foundation of America. JAMA 1993
  270854-859.
• The neurodiagnostic evaluation of the child with
  first simple febrile seizure. AAP. Pediatrics
  1996 97769-775.
• 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 55616-623.
• Role of antiseizure prophylaxis following head
  injury. BTF / AANS. J Neurotrauma 2000
  17549-553.
• Treatment of the child with a first unprovoked
  seizure. AAN. Neurology 2003 60166-175
• Antiepileptic drug prophylaxis in severe
  traumatic brain injury. Neurology 2003 6010-16

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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

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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

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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 lt1 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

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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

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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 19373-377. Prospective. 136
patients) Nypaver. ED laboratory evaluation of
hcildren with seizures Dogma or dilemma? Ped
Emerg Care 1992 813-21. Retrospective 308
patients)
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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 (gt5 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
5905-911. Retrospective review, 26
patients Green S,. Can seizures be the sole
manifestation of meningitis in febrile children?
Pediatrics 1993 92527-534. Retrospective. 503
cases
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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

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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 131-5. Retrospective review.
247 patients. Henneman AEM 1994 241108-1114.
Retrospective. 294 patients).
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Neuroimaging in New Onset Seizures

• ACEP, AAN, AANS, ASNR. Practice Parameter ED
  neuroimaging in the seizure pt. Ann Emerg Med
  1996 27114-118. 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

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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

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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

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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

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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 14789-92 Van der
Meyden. Epilepsia 1994 35189-194
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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.

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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

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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

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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 199233829-835 DeLorenzo.
Epilepsia 1998 39833-840
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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
1993270854-859
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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 1998339792-798
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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 43146-153.
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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.

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DIFFERENTIAL DIAGNOSIS OF PROLONGED POSTICTAL
STATE

• Intracranial catastrophe
• Hypoglycemia
• Drug effect
• SCSE
• NCSE

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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.

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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