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ANN EMERG MED. 2014;63:437-447.
ACEP Clinical Policy
Critical Issues in the
Evaluation and Management
of Adult Patients Presenting
to the Emergency Department
With Seizures
The American College of Emergency
Physicians’ (ACEP) 2004 clinical policy on
seizures addressed 2 critical questions on
laboratory testing and neuroimaging:
1. What laboratory tests are
indicated in the otherwise healthy
adult patient with a newonset
seizure who has returned to a
baseline normal neurologic status?
2. Which new-onset seizure patients
who have returned to a normal
baseline require a head CT in the
ED?
This clinical policy from
the ACEP is the revision
of a 2004 policy on
critical issues in the
evaluation and
management of adult
patients with seizures in
the ED to help clinicians
answer the following
critical questions:
In patients with a first
generalized convulsive
seizure who have
returned to their
baseline clinical status,
should antiepileptic
therapy be initiated in
the ED to prevent
additional seizures?
In patients with a first
unprovoked seizure who
have returned to their
baseline clinical status
in the ED, should the
patient be admitted to
the hospital to prevent
adverse events?
In patients with a known
seizure disorder in
which resuming their
antiepileptic medication
in the ED is deemed
appropriate, does the
route of administration
impact recurrence of
seizures?
In ED patients with
generalized convulsive
status epilepticus who
continue to have seizures
despite receiving optimal
dosing of a
benzodiazepine, which
agent or agents should
be administered next to
terminate seizures?
Classification of Seizures
Provoked seizure
–acute symptomatic seizure
Unprovoked seizure
–including remote symptomatic
seizure
Provoked seizure
Definition
Provoked seizure equivalent to acute
symptomatic seizure; seizure occurs at time
of or within 7 days of an acute neurologic,
systemic, metabolic, or toxic insult
Examples
Seizures from hyponatremia or other
electrolyte abnormalities, withdrawal, toxic
ingestions, encephalitis, CNS mass lesions,
and many others
Unprovoked seizure
Definition
Seizure occurs without acute precipitating
factors; unprovoked seizures include but are
not limited to remote symptomatic seizures if
seizure is thought to result from CNS or
systemic insult that occurred more than 7 days
in the past
Examples
Idiopathic seizures; epilepsy (if recurrent);
seizure attributed to history of stroke,
traumatic brain injury, or other past events
Classes of Evidence to
Recommendation Levels
Level A recommendations
Generally accepted principles for patient care that
reflect a high degree of clinical certainty
Level B recommendations
Recommendations for patient care that may
identify a particular strategy or range of
strategiesthat reflect moderate clinical certainty
Level C recommendations
Recommendations for patient care that are based
on evidence from Class of Evidence III studies or,
in the absence of any adequate published
literature, based on expert consensus
Scope of Application
This guideline is intended for physicians
working in EDs
Inclusion Criteria
This guideline is intended for adult patients
aged 18 years and older presenting to the ED
with generalized convulsive seizures
Exclusion Criteria
This guideline is not intended for pediatric
patients, patients with complex partial
seizures, patients with acute head trauma or
multisystem trauma, patients with brain mass
or brain tumor, immunocompromised patients,
or patients with eclampsia
Critical
Questions
In patients with a first
generalized convulsive
seizure who have
returned to their
baseline clinical status,
should antiepileptic
therapy be initiated in
the ED to prevent
additional seizures?
Level C recommendations
1. Emergency physicians need not
initiate antiepileptic medication*
in the ED for patients who have
had a first provoked seizure.
Precipitating medical conditions
should be identified and treated.
* Antiepileptic medication in this
document refers to medications
prescribed for seizure prevention.
Level C recommendations
2. Emergency physicians need not
initiate antiepileptic medication*
in the ED for patients who have
had a first unprovoked seizure
without evidence of brain disease
or injury.
Level C recommendations
3. Emergency physicians may
initiate antiepileptic medication*
in the ED, or defer in
coordination with other providers,
for patients who experienced a
first unprovoked seizure with a
remote history of brain disease or
injury.
In patients with a first
unprovoked seizure who
have returned to their
baseline clinical status
in the ED, should the
patient be admitted to
the hospital to prevent
adverse events?
Level C recommendations
Emergency physicians need not
admit patients with a first
unprovoked seizure who have
returned to their clinical baseline
in the ED.
Dunn et al proposed a disposition algorithm for
patients with uncomplicated first generalized
seizure that uses glucose, CT scan (if
indicated and done), ECG, and blood tests
for renal function, electrolyte level,
calcium level, and blood count.
They proposed that the patient with normal
results may be discharged, provided the
following criteria are satisfied: full recovery
without abnormal neurologic signs and/or
symptoms, normal vital signs, received
advice not to drive, availability of a
responsible adult to watch him or her, follow-
up arranged, and follow-up likely.
Emerg Med J 2005;22:237–242
In patients with a known
seizure disorder in
which resuming their
antiepileptic medication
in the ED is deemed
appropriate, does the
route of administration
impact recurrence of
seizures?
Level C recommendations
When resuming antiepileptic
medication in the ED is deemed
appropriate, the emergency
physician may administer IV or
oral medication at their discretion.
Loading dose and route of
administration strategies
for antiepileptic
medications in the ED
Carbamazepine
(Tegretol, Equetro)
Loading Dose
8 mg/kg oral suspension, single oral load;
IV not available
Adverse Effects
Common drowsiness, nausea, dizziness
Notes
Oral tablet has slow/erratic absorption
Gabapentin (Neurontin, Gralise)
Loading Dose
900 mg/day oral (300 mg tid) for 3 days; IV
not available
Adverse Effects
Somnolence, dizziness, ataxia, and fatigue
Notes
Adjunct for partial seizures
Lamotrigine (Lamictal)
Loading Dose
6.5 mg/kg single oral load if on lamotrigine for
>6 mo without a history of rash or intolerance
in the past and only off lamotrigine for <5
days; IV not available
Adverse Effects
Mild, transient nausea
Notes
Frequent and serious rashes; do not load if
history of rash or patient not previously on
lamotrigine
Levetiracetam (Keppra)
Loading Dose
1,500 mg oral load; rapid IV loading safe and
well tolerated in doses up to 60 mg/kg
Adverse Effects
Fatigue, dizziness, rarely pain at infusion site
Notes
Frequent and serious rashes; do not load if
history of rash or patient not previously on
lamotrigine
Phenytoin (Dilantin, Phenytek)
Loading Dose
20 mg/kg divided in maximum doses of 400 mg
every 2 h orally, or 18 mg/kg IV at maximum rate
of 50 mg/min
Adverse Effects
IV is faster to load but more serious adverse
effects than oral, including hypotension,
bradyarrhythmias, cardiac arrest, and
extravasation injuries
Notes
Oral is cheaper but takes >5 h to reach
therapeutic levels; IV requires filter, infusion pump
Fosphenytoin (Cerebyx)
Loading Dose
18 PE/kg IV at maximum rate of 150 PE/min;
IM administration possible
Adverse Effects
Fewer adverse events in head-to-head
analysis between IV fosphenytoin and IV
phenytoin load
Notes
Generic now available with significant cost
reduction
Valproate (Depacon)
Loading Dose
Up to 30 mg/kg IV at max rate of 10
mg/kg/min IV
Adverse Effects
Transient local irritation at injection site
In ED patients with
generalized convulsive
status epilepticus who
continue to have seizures
despite receiving optimal
dosing of a
benzodiazepine, which
agent or agents should
be administered next to
terminate seizures?
Level A recommendations
Emergency physicians should
administer an additional
antiepileptic medication in ED
patients with refractory status
epilepticus who have failed
treatment with benzodiazepines.
Level B recommendations
Emergency physicians may
administer intravenous phenytoin,
fosphenytoin, or valproate in
ED patients with refractory status
epilepticus who have failed
treatment with benzodiazepines.
Level C recommendations
Emergency physicians may
administer intravenous
levetiracetam, propofol, or
barbiturates in ED patients with
refractory status epilepticus who
have failed treatment with
benzodiazepines.
Patients who continue to have generalized
convulsive status epilepticus failed first-line
treatment with optimal dosing of
benzodiazepines should be given an
additional anticonvulsant agent.
Simultaneously, one should search for treatable
causes of status epilepticus, including
hypoglycemia, hyponatremia, hypoxia, drug
toxicity, withdrawal syndromes, systemic or
CNS infection, ischemic stroke, intracerebral
hemorrhage.
If a provoking cause is discovered for status
epilepticus, condition-specific treatment
should be given.
The Neurocritical Care Society’s Status
Epilepticus Guideline Writing Committee
recommended urgent control of seizures
with any of the following: valproate,
levetiracetam, or phenobarbital, in
addition to phenytoin/fosphenytoin.
Valproate was recommended for both
emergent treatment of seizures and
refractory status epilepticus based on
high-level evidence.
Neurocrit Care. 2012;17:3-23.
The European Federation of Neurological
Societies’ evidence-based guideline for
status epilepticus in adults recommended
anesthetic doses of midazolam, propofol,
or barbiturates for status epilepticus
refractory to benzodiazepines and
phenytoin.
Eur J Neurol. 2010;17:346-355.
IV medication options for
generalized convulsive
status epilepticus
Phenytoin (Dilantin, Phenytek)
Dose
18-20 mg/kg administered no faster than
50 mg/kg; some recommend to increase to
total 30 mg/kg if seizures continue
Adverse Effects
Soft tissue injury with extravasation,
hypotension, cardiac dysrhythmias, purple
glove syndrome
Fosphenytoin (Cerebyx)
Dose
18-20 PE/kg administered no faster than
150 PE/min
Adverse Effects
Hypotension, cardiac dysrhythmias
Valproate (Depacon)
Dose
20 to 30 mg/kg at rate of 40 mg/min (faster
administration rates also reported)
Adverse Effects
Dizziness, thrombocytopenia, liver toxicity,
hyperammonemia
Levetiracetam (Keppra)
Dose
30–50 mg/kg IV load at 100 mg/min
Adverse Effects
Nausea, rash
Propofol (Diprivan)
Dose
2 mg/kg; may repeat in 3-5 min;
maintenance infusion of 5 mg/kg/h
Adverse Effects
Injection site pain, heart failure, respiratory
support required
Phenobarbital (Luminal)
Dose
10-20 mg/kg; may repeat 5-10 mg/kg at 10
min
Adverse Effects
Respiratory depression, hypotension
Valproate works as well in status
epilepticus after benzodiazepine
administration as a second-line agent as
phenytoin and fosphenytoin.
Levetiracetam is safe, with low
incidence of hypotension and respiratory
depression when given as an IV load.
Propofol can be useful in intubated
patients who continue to seize, provided
they do not exhibit hypotension.
Questions ?

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Management of Seizures in ED

  • 1. ANN EMERG MED. 2014;63:437-447. ACEP Clinical Policy Critical Issues in the Evaluation and Management of Adult Patients Presenting to the Emergency Department With Seizures
  • 2. The American College of Emergency Physicians’ (ACEP) 2004 clinical policy on seizures addressed 2 critical questions on laboratory testing and neuroimaging: 1. What laboratory tests are indicated in the otherwise healthy adult patient with a newonset seizure who has returned to a baseline normal neurologic status? 2. Which new-onset seizure patients who have returned to a normal baseline require a head CT in the ED?
  • 3. This clinical policy from the ACEP is the revision of a 2004 policy on critical issues in the evaluation and management of adult patients with seizures in the ED to help clinicians answer the following critical questions:
  • 4. In patients with a first generalized convulsive seizure who have returned to their baseline clinical status, should antiepileptic therapy be initiated in the ED to prevent additional seizures?
  • 5. In patients with a first unprovoked seizure who have returned to their baseline clinical status in the ED, should the patient be admitted to the hospital to prevent adverse events?
  • 6. In patients with a known seizure disorder in which resuming their antiepileptic medication in the ED is deemed appropriate, does the route of administration impact recurrence of seizures?
  • 7. In ED patients with generalized convulsive status epilepticus who continue to have seizures despite receiving optimal dosing of a benzodiazepine, which agent or agents should be administered next to terminate seizures?
  • 8. Classification of Seizures Provoked seizure –acute symptomatic seizure Unprovoked seizure –including remote symptomatic seizure
  • 9. Provoked seizure Definition Provoked seizure equivalent to acute symptomatic seizure; seizure occurs at time of or within 7 days of an acute neurologic, systemic, metabolic, or toxic insult Examples Seizures from hyponatremia or other electrolyte abnormalities, withdrawal, toxic ingestions, encephalitis, CNS mass lesions, and many others
  • 10. Unprovoked seizure Definition Seizure occurs without acute precipitating factors; unprovoked seizures include but are not limited to remote symptomatic seizures if seizure is thought to result from CNS or systemic insult that occurred more than 7 days in the past Examples Idiopathic seizures; epilepsy (if recurrent); seizure attributed to history of stroke, traumatic brain injury, or other past events
  • 11. Classes of Evidence to Recommendation Levels Level A recommendations Generally accepted principles for patient care that reflect a high degree of clinical certainty Level B recommendations Recommendations for patient care that may identify a particular strategy or range of strategiesthat reflect moderate clinical certainty Level C recommendations Recommendations for patient care that are based on evidence from Class of Evidence III studies or, in the absence of any adequate published literature, based on expert consensus
  • 12. Scope of Application This guideline is intended for physicians working in EDs Inclusion Criteria This guideline is intended for adult patients aged 18 years and older presenting to the ED with generalized convulsive seizures Exclusion Criteria This guideline is not intended for pediatric patients, patients with complex partial seizures, patients with acute head trauma or multisystem trauma, patients with brain mass or brain tumor, immunocompromised patients, or patients with eclampsia
  • 14. In patients with a first generalized convulsive seizure who have returned to their baseline clinical status, should antiepileptic therapy be initiated in the ED to prevent additional seizures?
  • 15. Level C recommendations 1. Emergency physicians need not initiate antiepileptic medication* in the ED for patients who have had a first provoked seizure. Precipitating medical conditions should be identified and treated. * Antiepileptic medication in this document refers to medications prescribed for seizure prevention.
  • 16. Level C recommendations 2. Emergency physicians need not initiate antiepileptic medication* in the ED for patients who have had a first unprovoked seizure without evidence of brain disease or injury.
  • 17. Level C recommendations 3. Emergency physicians may initiate antiepileptic medication* in the ED, or defer in coordination with other providers, for patients who experienced a first unprovoked seizure with a remote history of brain disease or injury.
  • 18. In patients with a first unprovoked seizure who have returned to their baseline clinical status in the ED, should the patient be admitted to the hospital to prevent adverse events?
  • 19. Level C recommendations Emergency physicians need not admit patients with a first unprovoked seizure who have returned to their clinical baseline in the ED.
  • 20. Dunn et al proposed a disposition algorithm for patients with uncomplicated first generalized seizure that uses glucose, CT scan (if indicated and done), ECG, and blood tests for renal function, electrolyte level, calcium level, and blood count. They proposed that the patient with normal results may be discharged, provided the following criteria are satisfied: full recovery without abnormal neurologic signs and/or symptoms, normal vital signs, received advice not to drive, availability of a responsible adult to watch him or her, follow- up arranged, and follow-up likely. Emerg Med J 2005;22:237–242
  • 21. In patients with a known seizure disorder in which resuming their antiepileptic medication in the ED is deemed appropriate, does the route of administration impact recurrence of seizures?
  • 22. Level C recommendations When resuming antiepileptic medication in the ED is deemed appropriate, the emergency physician may administer IV or oral medication at their discretion.
  • 23. Loading dose and route of administration strategies for antiepileptic medications in the ED
  • 24. Carbamazepine (Tegretol, Equetro) Loading Dose 8 mg/kg oral suspension, single oral load; IV not available Adverse Effects Common drowsiness, nausea, dizziness Notes Oral tablet has slow/erratic absorption
  • 25. Gabapentin (Neurontin, Gralise) Loading Dose 900 mg/day oral (300 mg tid) for 3 days; IV not available Adverse Effects Somnolence, dizziness, ataxia, and fatigue Notes Adjunct for partial seizures
  • 26. Lamotrigine (Lamictal) Loading Dose 6.5 mg/kg single oral load if on lamotrigine for >6 mo without a history of rash or intolerance in the past and only off lamotrigine for <5 days; IV not available Adverse Effects Mild, transient nausea Notes Frequent and serious rashes; do not load if history of rash or patient not previously on lamotrigine
  • 27. Levetiracetam (Keppra) Loading Dose 1,500 mg oral load; rapid IV loading safe and well tolerated in doses up to 60 mg/kg Adverse Effects Fatigue, dizziness, rarely pain at infusion site Notes Frequent and serious rashes; do not load if history of rash or patient not previously on lamotrigine
  • 28. Phenytoin (Dilantin, Phenytek) Loading Dose 20 mg/kg divided in maximum doses of 400 mg every 2 h orally, or 18 mg/kg IV at maximum rate of 50 mg/min Adverse Effects IV is faster to load but more serious adverse effects than oral, including hypotension, bradyarrhythmias, cardiac arrest, and extravasation injuries Notes Oral is cheaper but takes >5 h to reach therapeutic levels; IV requires filter, infusion pump
  • 29. Fosphenytoin (Cerebyx) Loading Dose 18 PE/kg IV at maximum rate of 150 PE/min; IM administration possible Adverse Effects Fewer adverse events in head-to-head analysis between IV fosphenytoin and IV phenytoin load Notes Generic now available with significant cost reduction
  • 30. Valproate (Depacon) Loading Dose Up to 30 mg/kg IV at max rate of 10 mg/kg/min IV Adverse Effects Transient local irritation at injection site
  • 31. In ED patients with generalized convulsive status epilepticus who continue to have seizures despite receiving optimal dosing of a benzodiazepine, which agent or agents should be administered next to terminate seizures?
  • 32. Level A recommendations Emergency physicians should administer an additional antiepileptic medication in ED patients with refractory status epilepticus who have failed treatment with benzodiazepines.
  • 33. Level B recommendations Emergency physicians may administer intravenous phenytoin, fosphenytoin, or valproate in ED patients with refractory status epilepticus who have failed treatment with benzodiazepines.
  • 34. Level C recommendations Emergency physicians may administer intravenous levetiracetam, propofol, or barbiturates in ED patients with refractory status epilepticus who have failed treatment with benzodiazepines.
  • 35. Patients who continue to have generalized convulsive status epilepticus failed first-line treatment with optimal dosing of benzodiazepines should be given an additional anticonvulsant agent. Simultaneously, one should search for treatable causes of status epilepticus, including hypoglycemia, hyponatremia, hypoxia, drug toxicity, withdrawal syndromes, systemic or CNS infection, ischemic stroke, intracerebral hemorrhage. If a provoking cause is discovered for status epilepticus, condition-specific treatment should be given.
  • 36. The Neurocritical Care Society’s Status Epilepticus Guideline Writing Committee recommended urgent control of seizures with any of the following: valproate, levetiracetam, or phenobarbital, in addition to phenytoin/fosphenytoin. Valproate was recommended for both emergent treatment of seizures and refractory status epilepticus based on high-level evidence. Neurocrit Care. 2012;17:3-23.
  • 37. The European Federation of Neurological Societies’ evidence-based guideline for status epilepticus in adults recommended anesthetic doses of midazolam, propofol, or barbiturates for status epilepticus refractory to benzodiazepines and phenytoin. Eur J Neurol. 2010;17:346-355.
  • 38. IV medication options for generalized convulsive status epilepticus
  • 39. Phenytoin (Dilantin, Phenytek) Dose 18-20 mg/kg administered no faster than 50 mg/kg; some recommend to increase to total 30 mg/kg if seizures continue Adverse Effects Soft tissue injury with extravasation, hypotension, cardiac dysrhythmias, purple glove syndrome
  • 40. Fosphenytoin (Cerebyx) Dose 18-20 PE/kg administered no faster than 150 PE/min Adverse Effects Hypotension, cardiac dysrhythmias
  • 41. Valproate (Depacon) Dose 20 to 30 mg/kg at rate of 40 mg/min (faster administration rates also reported) Adverse Effects Dizziness, thrombocytopenia, liver toxicity, hyperammonemia
  • 42. Levetiracetam (Keppra) Dose 30–50 mg/kg IV load at 100 mg/min Adverse Effects Nausea, rash
  • 43. Propofol (Diprivan) Dose 2 mg/kg; may repeat in 3-5 min; maintenance infusion of 5 mg/kg/h Adverse Effects Injection site pain, heart failure, respiratory support required
  • 44. Phenobarbital (Luminal) Dose 10-20 mg/kg; may repeat 5-10 mg/kg at 10 min Adverse Effects Respiratory depression, hypotension
  • 45. Valproate works as well in status epilepticus after benzodiazepine administration as a second-line agent as phenytoin and fosphenytoin. Levetiracetam is safe, with low incidence of hypotension and respiratory depression when given as an IV load. Propofol can be useful in intubated patients who continue to seize, provided they do not exhibit hypotension.