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Status Epilepticus
Dr. Ravindra K. Sharma
Pediatric Specialist
“Status

epilepticus is a medical
emergency that requires an organized
and skillful approach to minimize the
associated mortality and morbidity”
• Status epilepticus (SE) presents in a multitude
of forms, dependent on etiology and patient
age (myoclonic, tonic, subtle, tonic-clonic,
absence, complex partial etc.)
• Generalized, tonic-clonic SE is the most
common form of SE.
Definition:
• Conventional definition:
–Single seizure > 30 minutes
–Series of seizures > 30 minutes without
full recovery
Definition:….
– “If appropriate therapy is delayed, SE can
cause permanent neurologic sequelae or
death …”
thus
– “ … any child who presents actively convulsing
should be assumed to have SE.”
Haafiz A. Pediatr Emerg Care 1999;15(2):119-29
The longer SE persists,
–the lower is the likelihood of spontaneous
cessation
–the harder is it to control
–the higher is the risk of morbidity and
mortality
Treatment for most seizures needs to be
instituted after > 5 minutes of seizure activity
Bleck TP. Epilepsia 1999;40(1):S64-6
But
• This is not practical operational definition.
• Longer periods with uncontrolled seizure
activity, more likely to develop a RSE
syndrome.
• More practical guidelines needed to draw that
arbitrary ‘line in sand’, beyond which
substantial risk of developing clinical SE exists.
Operational Definition:

“Continuous seizures lasting at least 5 minutes
or two or more discrete seizures between which
there is an incomplete recovery of
consciousness”
Causes.
•
•
•
•
•
•
•

Fever
Medication change
Unknown
Metabolic
Congenital
Anoxic
Other (trauma, vascular,
infection, tumor,
drugs,endocrine)

DeLorenzo RJ. Epilepsia 1992;33 Suppl 4:S15-25

36 %
20 %
9 %
8%
7 %
5 %
15 %
Pathophysiology
• GLUTAMATE = the major excitatory AA
neurotransmitter in brain
– Any factor increases Glutamate activity can lead to
seizures
– NMDA(N-methyl-D-aspartic acid) is an AA derivative
which acts as a specific agonist at the NMDA receptor
mimicking the action of glutamate
• GABA = main inhibitory neurotransmitter, ; GABA
antagonists can cause SE
Drugs which can cause seizures
• Antibiotics
– Penicillins
– Isoniazid
– Metronidazole
• Anesthetics, narcotics
– Halothane, enflurane
– Cocaine, fentanyl
– Ketamine

• Psychopharmaceuticals
– Antihistamines
– Antidepressants
– Antipsychotics
– Phencyclidine
– Tricyclic antidepressants
– List of drugs
Mortality

• Adults
• Children

15 to 22%
3 to 15%

Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23-30
Prolonged seizures
Temporary
systemic
changes

Life
threatening
systemic
changes

Duration of seizure

Death
Respiratory
• Hypoxia and hypercarbia
- ⇓ ventilation (chest rigidity from muscle spasm)
- Hypermetabolism (⇑ O2 consumption, ⇑ CO2 production)
- Poor handling of secretions
- Neurogenic pulmonary edema?
Hypoxia
• Hypoxia/anoxia markedly increase the risk of
mortality in SE
• Seizures (without hypoxia) are much less dangerous
than seizures and hypoxia
Towne AR. Epilepsia 1994;35(1):27-34
Neurogenic pulmonary edema
•Rare complication
•Likely occurs as
consequence of marked
increase of pulmonary
vascular pressure

Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases.
Epilepsia 1996;37(5):428-32
Acidosis
• Respiratory
• Lactic
– Impaired tissue oxygenation
– Increased energy expenditure
Hemodynamics
• Sympathetic overdrive
– Massive
catecholamine /
autonomic discharge
– Hypertension
– Tachycardia
– High CVP

0 min



60 min

Exhaustion
 Hypotension
 Hypoperfusion
Cerebral blood flow - Cerebral O2 requirement
• Hyperdynamic phase
O2 requirement

– CBF meets CMRO2

• Exhaustion phase
Blood flow
Blood pressure

Seizure duration

– CBF drops as
hypotension sets in
– Autoregulation
exhausted
– Neuronal damage ensues
Glucose

Glucose

• Hyperdynamic
phase
– Hyperglycemia

• Exhaustion phase
SE

30 min

SE + hypoxia

Seizure duration

– Hypoglycemia
develops
– Hypoglycemia appears
earlier in presence of
hypoxia
– Neuronal damage
ensues
Hyperpyrexia
• Hyperpyrexia may develop during protracted
SE, and aggravate possible mismatch of
cerebral metabolic requirement and substrate
delivery
• Treat hyperpyrexia aggressively
– Antipyretics, external cooling
Other alterations
•
•
•
•
•

Blood leukocytosis (50% of children)
Spinal fluid leukocytosis (15% of children)
⇑ K+
⇑ creatine kinase
Myoglobinuria
Acute Management of Seizures
Common Sense:0-5 minutes
Stabilize the patient-

A

Oxygen, oral airway. Avoid hypoxia!

B

Consider bag-valve mask ventilation.
Consider intubation

C

IV/IO access. Treat hypotension, but NOT
hypertension
(0-5 minutes)…
• Arterial blood gas?
– All children in SE have acidosis. It often resolves rapidly
with termination of SE

• Intubate?
– It may be difficult to intubate the actively seizing child
– Stop or slow seizures first, give O2, consider BVM
ventilation
– If using paralytic agent to intubate, assume that SE
continues
0-5 minutes….
Give glucose (2-4 ml/kg D25%, infants 5 ml/kg D10%), unless
normo- or hyperglycemic
Hyperglycemia has no negative effect in SE
(as long as significant hyperosmolality is being avoided)

Adoloscent-Thiamin 100 mg IV first
Initial investigations(0-5 minutes)….
• Labs
–
–
–
–
–
–

Na,K, Ca, Mg, PO4 , BUN, Cret, glucose
CBC
Liver function tests, ammonia
Anticonvulsant level
Toxicology
Blood C/S

• Initial screening history and Physical examination
Work-Up (when stable)
• Lumbar puncture
– Always defer LP in unstable patient, but never delay
antibiotic/antiviral rx if indicated

• CT scan/MRI scan
– Indicated for focal seizures or deficit, history of trauma or
bleeding d/o

• EEG
Treatment (Pharmacotheraqpy)
5-15 minutes..
• The longer we wait with anticonvulsant, the
more anticonvulsant we will need to stop SE
• Most common mistake is ineffective dose
Anticonvulsants
• Rapid acting

plus
• Long acting
Anticonvulsants - Rapid acting
• Benzodiazepines
– Lorazepam 0.05- 0.1 mg/kg i.v.(rectal dose same) upto 46 mg over 1-2 minutes
or
– Diazepam 0.2- 0.5 mg/kg i.v. upto 6-10mg over 1-2
minutes
– Diazepam 0.5 mg/kg rectally
– Midazolam 0.15-0.3 mg/kg IV ; nasal or Buccal (0.5
mg/kg) is used if no IV line
– If SE persists, repeat every 5-10 minutes
Benzodiazepines
• Lorazepam
–
–
–
–

Low lipid solubility
Action delayed 2 minutes
Anticonvulsant effect 6-12 hrs
Less respiratory depression than
diazepam

Midazolam
for brief seizures
May be given i.m.
 to treat refractory SE

• Diazepam
–
–
–
–

High lipid solubility
Thus very rapid onset
Redistributes rapidly
Thus rapid loss of
anticonvulsant effect
– Adverse effects are
persistent:
• Hypotension
• Resp. depression
Anticonvulsants :15-35 minutes
(If seizures persists)
• Phenytoin
– 15-20 mg/kg i.v. over 15-20
min
– pH 12
Extravasation causes severe
tissue injury
– Onset 10-30 min
– May cause hypotension,
dysrhythmia
– Dilute with Dext. free solution
– Cheap

• Fosphenytoin
– 15-20 mg PE/kg i.v./i.m. over 57 min PE = phenytoin equivalent
– Fosphenytoin 150 mg is equal to 100
mg phenytoin

– pH 8.6
Extravasation well tolerated
– Onset 5-10 min
– May cause hypotension
– Expensive
Anticonvulsants :(15-35 minutes)
• Phenobarbital
– 15-20 mg/kg (neonate 20-30 mg/kg)i.v. over
15-20 min
– Onset 15-30 min
– May cause hypotension, respiratory
depression
Initial choice of long acting anticonvulsants in
SE
Is patient an infant?
Is patient already receiving phenytoin?
No

At high risk for extravasation ?

Yes

Phenobarbital

(small vein, difficult access etc.)?
No

Phenytoin

Preffered in Cardiac patient,
Head trauma,

Yes

Fosphenytoin
If SE persists (45 minutes)
• Phenobarbital if Phenytoin used
• Additional phenytoin or FP 5 mg/kg (Nelson 10 mg/kg
increment) max upto 30 mg ,
• Additional phenobarbital 5 mg/kg/dose every 15–30
min (max total dose of 30 mg/kg)
• be prepared to support respirations
• Consider IV valproate, especially for partial status
epilepticus
Seizures Persists (60 minutes)
• Consider Diazepam infusion, pentobarbital
(Barbiturate coma), midazolam, paraldehyde
or general anesthesia infusion in PICU
• Midazolam 0.2 mg/kg bolus & 20-400
mcg/kg/hr infusion
• Propofol 1-2 mg/kg then 2-10 mg/kg/hr
infusion
• Avoid paralytics
Still Seizures Persists….
• Induction of Barbiturate coma for 48 hrs
• IV loading thiopental 2–4 mg/kg till a burst
suppression EEG pattern till 48 hrs
• check phenobarbital level to be normal.
• Paraldehyde :loading 150–200 mg/kg IV for 15–20
min, then 20 mg/kg/hr in a 5% concentration in a
glass bottle freshly prepared
Still Seizures Persists….
• General anesthesia: if barbiturate coma is not
option.
– halothane and Isoflurane.
– Acts by reversing cerebral anoxia and metabolic
abnormalities, allowing the previously
administered anticonvulsants to exert their effect.
Possible new drugs for Status
• Lidocaine - some positive trials
• Valproate - IV form available
• 10-15 mg/kg IV.
• Gabapentin / Vigabatrin / Lamotrigine
• Felbamate - blocks NMDA receptors
• Ketamine - blocks NMDA receptors
Use of AED after status episode is controversial especially
idiopathic or febrile seizure.
Non - convulsive status epilepticus?
• NCSE is a term used to denote a range of conditions in
which electrographic seizure activity is prolonged and
results in non convulsive clinical symptoms.
Non - convulsive SE ?

• Up to 20 % of children with SE have non convulsive SE after tonic - clonic SE
Non - convulsive SE ?

• If child does not begin to respond to painful
stimuli within 20 - 30 minutes after tonic clonic SE, suspect non - convulsive SE
– Urgent EEG
Summary
• Status Epilepticus is >5 min of seizures or two seizures
without return to consciousness
• Status Epilepticus is common
• Delay in therapy makes SE harder to rest
• Mortality and morbidity is increased in prolonged SE
• BZD, Pheny/Pheno, Call for PICU
• Status Epilepticus needs a DIAGNOSIS
Take-Home points • Better outcome if seizure stopped earlier, so no need to
wait
• Always ABC D FIRST
• Lorazepam - best 1st line Rx
• Fosphenytoin - surpasses Phenytoin for SE, and can be
given IM in difficult situation
• Propofol - advantages over barbiturates for resistant SE,
low toxicity , quick action, and fast recovery upon
discontinuation

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Status epilapticus print

  • 1. Status Epilepticus Dr. Ravindra K. Sharma Pediatric Specialist
  • 2. “Status epilepticus is a medical emergency that requires an organized and skillful approach to minimize the associated mortality and morbidity”
  • 3. • Status epilepticus (SE) presents in a multitude of forms, dependent on etiology and patient age (myoclonic, tonic, subtle, tonic-clonic, absence, complex partial etc.) • Generalized, tonic-clonic SE is the most common form of SE.
  • 4. Definition: • Conventional definition: –Single seizure > 30 minutes –Series of seizures > 30 minutes without full recovery
  • 5. Definition:…. – “If appropriate therapy is delayed, SE can cause permanent neurologic sequelae or death …” thus – “ … any child who presents actively convulsing should be assumed to have SE.” Haafiz A. Pediatr Emerg Care 1999;15(2):119-29
  • 6. The longer SE persists, –the lower is the likelihood of spontaneous cessation –the harder is it to control –the higher is the risk of morbidity and mortality Treatment for most seizures needs to be instituted after > 5 minutes of seizure activity Bleck TP. Epilepsia 1999;40(1):S64-6
  • 7. But • This is not practical operational definition. • Longer periods with uncontrolled seizure activity, more likely to develop a RSE syndrome. • More practical guidelines needed to draw that arbitrary ‘line in sand’, beyond which substantial risk of developing clinical SE exists.
  • 8. Operational Definition: “Continuous seizures lasting at least 5 minutes or two or more discrete seizures between which there is an incomplete recovery of consciousness”
  • 9. Causes. • • • • • • • Fever Medication change Unknown Metabolic Congenital Anoxic Other (trauma, vascular, infection, tumor, drugs,endocrine) DeLorenzo RJ. Epilepsia 1992;33 Suppl 4:S15-25 36 % 20 % 9 % 8% 7 % 5 % 15 %
  • 10. Pathophysiology • GLUTAMATE = the major excitatory AA neurotransmitter in brain – Any factor increases Glutamate activity can lead to seizures – NMDA(N-methyl-D-aspartic acid) is an AA derivative which acts as a specific agonist at the NMDA receptor mimicking the action of glutamate • GABA = main inhibitory neurotransmitter, ; GABA antagonists can cause SE
  • 11. Drugs which can cause seizures • Antibiotics – Penicillins – Isoniazid – Metronidazole • Anesthetics, narcotics – Halothane, enflurane – Cocaine, fentanyl – Ketamine • Psychopharmaceuticals – Antihistamines – Antidepressants – Antipsychotics – Phencyclidine – Tricyclic antidepressants – List of drugs
  • 12. Mortality • Adults • Children 15 to 22% 3 to 15% Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23-30
  • 14. Respiratory • Hypoxia and hypercarbia - ⇓ ventilation (chest rigidity from muscle spasm) - Hypermetabolism (⇑ O2 consumption, ⇑ CO2 production) - Poor handling of secretions - Neurogenic pulmonary edema?
  • 15. Hypoxia • Hypoxia/anoxia markedly increase the risk of mortality in SE • Seizures (without hypoxia) are much less dangerous than seizures and hypoxia Towne AR. Epilepsia 1994;35(1):27-34
  • 16. Neurogenic pulmonary edema •Rare complication •Likely occurs as consequence of marked increase of pulmonary vascular pressure Johnston SC. Postictal pulmonary edema requires pulmonary vascular pressure increases. Epilepsia 1996;37(5):428-32
  • 17. Acidosis • Respiratory • Lactic – Impaired tissue oxygenation – Increased energy expenditure
  • 18. Hemodynamics • Sympathetic overdrive – Massive catecholamine / autonomic discharge – Hypertension – Tachycardia – High CVP 0 min  60 min Exhaustion  Hypotension  Hypoperfusion
  • 19. Cerebral blood flow - Cerebral O2 requirement • Hyperdynamic phase O2 requirement – CBF meets CMRO2 • Exhaustion phase Blood flow Blood pressure Seizure duration – CBF drops as hypotension sets in – Autoregulation exhausted – Neuronal damage ensues
  • 20. Glucose Glucose • Hyperdynamic phase – Hyperglycemia • Exhaustion phase SE 30 min SE + hypoxia Seizure duration – Hypoglycemia develops – Hypoglycemia appears earlier in presence of hypoxia – Neuronal damage ensues
  • 21. Hyperpyrexia • Hyperpyrexia may develop during protracted SE, and aggravate possible mismatch of cerebral metabolic requirement and substrate delivery • Treat hyperpyrexia aggressively – Antipyretics, external cooling
  • 22. Other alterations • • • • • Blood leukocytosis (50% of children) Spinal fluid leukocytosis (15% of children) ⇑ K+ ⇑ creatine kinase Myoglobinuria
  • 24. Common Sense:0-5 minutes Stabilize the patient- A Oxygen, oral airway. Avoid hypoxia! B Consider bag-valve mask ventilation. Consider intubation C IV/IO access. Treat hypotension, but NOT hypertension
  • 25. (0-5 minutes)… • Arterial blood gas? – All children in SE have acidosis. It often resolves rapidly with termination of SE • Intubate? – It may be difficult to intubate the actively seizing child – Stop or slow seizures first, give O2, consider BVM ventilation – If using paralytic agent to intubate, assume that SE continues
  • 26. 0-5 minutes…. Give glucose (2-4 ml/kg D25%, infants 5 ml/kg D10%), unless normo- or hyperglycemic Hyperglycemia has no negative effect in SE (as long as significant hyperosmolality is being avoided) Adoloscent-Thiamin 100 mg IV first
  • 27. Initial investigations(0-5 minutes)…. • Labs – – – – – – Na,K, Ca, Mg, PO4 , BUN, Cret, glucose CBC Liver function tests, ammonia Anticonvulsant level Toxicology Blood C/S • Initial screening history and Physical examination
  • 28. Work-Up (when stable) • Lumbar puncture – Always defer LP in unstable patient, but never delay antibiotic/antiviral rx if indicated • CT scan/MRI scan – Indicated for focal seizures or deficit, history of trauma or bleeding d/o • EEG
  • 29. Treatment (Pharmacotheraqpy) 5-15 minutes.. • The longer we wait with anticonvulsant, the more anticonvulsant we will need to stop SE • Most common mistake is ineffective dose
  • 31. Anticonvulsants - Rapid acting • Benzodiazepines – Lorazepam 0.05- 0.1 mg/kg i.v.(rectal dose same) upto 46 mg over 1-2 minutes or – Diazepam 0.2- 0.5 mg/kg i.v. upto 6-10mg over 1-2 minutes – Diazepam 0.5 mg/kg rectally – Midazolam 0.15-0.3 mg/kg IV ; nasal or Buccal (0.5 mg/kg) is used if no IV line – If SE persists, repeat every 5-10 minutes
  • 32. Benzodiazepines • Lorazepam – – – – Low lipid solubility Action delayed 2 minutes Anticonvulsant effect 6-12 hrs Less respiratory depression than diazepam Midazolam for brief seizures May be given i.m.  to treat refractory SE • Diazepam – – – – High lipid solubility Thus very rapid onset Redistributes rapidly Thus rapid loss of anticonvulsant effect – Adverse effects are persistent: • Hypotension • Resp. depression
  • 33. Anticonvulsants :15-35 minutes (If seizures persists) • Phenytoin – 15-20 mg/kg i.v. over 15-20 min – pH 12 Extravasation causes severe tissue injury – Onset 10-30 min – May cause hypotension, dysrhythmia – Dilute with Dext. free solution – Cheap • Fosphenytoin – 15-20 mg PE/kg i.v./i.m. over 57 min PE = phenytoin equivalent – Fosphenytoin 150 mg is equal to 100 mg phenytoin – pH 8.6 Extravasation well tolerated – Onset 5-10 min – May cause hypotension – Expensive
  • 34. Anticonvulsants :(15-35 minutes) • Phenobarbital – 15-20 mg/kg (neonate 20-30 mg/kg)i.v. over 15-20 min – Onset 15-30 min – May cause hypotension, respiratory depression
  • 35. Initial choice of long acting anticonvulsants in SE Is patient an infant? Is patient already receiving phenytoin? No At high risk for extravasation ? Yes Phenobarbital (small vein, difficult access etc.)? No Phenytoin Preffered in Cardiac patient, Head trauma, Yes Fosphenytoin
  • 36. If SE persists (45 minutes) • Phenobarbital if Phenytoin used • Additional phenytoin or FP 5 mg/kg (Nelson 10 mg/kg increment) max upto 30 mg , • Additional phenobarbital 5 mg/kg/dose every 15–30 min (max total dose of 30 mg/kg) • be prepared to support respirations • Consider IV valproate, especially for partial status epilepticus
  • 37. Seizures Persists (60 minutes) • Consider Diazepam infusion, pentobarbital (Barbiturate coma), midazolam, paraldehyde or general anesthesia infusion in PICU • Midazolam 0.2 mg/kg bolus & 20-400 mcg/kg/hr infusion • Propofol 1-2 mg/kg then 2-10 mg/kg/hr infusion • Avoid paralytics
  • 38. Still Seizures Persists…. • Induction of Barbiturate coma for 48 hrs • IV loading thiopental 2–4 mg/kg till a burst suppression EEG pattern till 48 hrs • check phenobarbital level to be normal. • Paraldehyde :loading 150–200 mg/kg IV for 15–20 min, then 20 mg/kg/hr in a 5% concentration in a glass bottle freshly prepared
  • 39. Still Seizures Persists…. • General anesthesia: if barbiturate coma is not option. – halothane and Isoflurane. – Acts by reversing cerebral anoxia and metabolic abnormalities, allowing the previously administered anticonvulsants to exert their effect.
  • 40. Possible new drugs for Status • Lidocaine - some positive trials • Valproate - IV form available • 10-15 mg/kg IV. • Gabapentin / Vigabatrin / Lamotrigine • Felbamate - blocks NMDA receptors • Ketamine - blocks NMDA receptors Use of AED after status episode is controversial especially idiopathic or febrile seizure.
  • 41. Non - convulsive status epilepticus? • NCSE is a term used to denote a range of conditions in which electrographic seizure activity is prolonged and results in non convulsive clinical symptoms.
  • 42. Non - convulsive SE ? • Up to 20 % of children with SE have non convulsive SE after tonic - clonic SE
  • 43. Non - convulsive SE ? • If child does not begin to respond to painful stimuli within 20 - 30 minutes after tonic clonic SE, suspect non - convulsive SE – Urgent EEG
  • 44. Summary • Status Epilepticus is >5 min of seizures or two seizures without return to consciousness • Status Epilepticus is common • Delay in therapy makes SE harder to rest • Mortality and morbidity is increased in prolonged SE • BZD, Pheny/Pheno, Call for PICU • Status Epilepticus needs a DIAGNOSIS
  • 45. Take-Home points • Better outcome if seizure stopped earlier, so no need to wait • Always ABC D FIRST • Lorazepam - best 1st line Rx • Fosphenytoin - surpasses Phenytoin for SE, and can be given IM in difficult situation • Propofol - advantages over barbiturates for resistant SE, low toxicity , quick action, and fast recovery upon discontinuation

Editor's Notes

  1. Based on a number of small studies mainly in children, felt that once these clinical parameters reached less likely for seizures to self-terminate. Still no generally accepted definition though.