Status Epilepticus
Dr. Ravindra K. Sharma
Pediatric Specialist
Fujairah Hospital, UAE
drravindrakr@yahoo.co.in
TAJ MAHAL, AGRA, INDIA
“Status

epilepticus is a medical
emergency that requires an organized
and skillful approach to minimize the
associated mo...
 Status epilepticus (SE)

presents in a multitude
of forms, dependent on etiology and patient
age (myoclonic, tonic, subt...
Definition:
 Conventional definition:

 Single

 Series

seizure > 30 minutes

of seizures > 30 minutes without
full re...
Definition:….
“If appropriate therapy is delayed, SE can
cause permanent neurologic sequelae or
death …”
thus




“ … an...
The longer SE persists,
the lower is the likelihood of spontaneous
cessation
the harder is it to control
the higher is ...
But
 This is

not practical operational definition.
 Longer periods with uncontrolled seizure
activity, more likely to d...
Operational Definition:

“Continuous seizures lasting at least 5 minutes
or two or more discrete seizures between which
th...
Causes.










Fever
Medication change
Unknown
Metabolic
Congenital
Anoxic
Other (trauma, vascular,
infection, t...
Pathophysiology
GLUTAMATE = the major excitatory AA
neurotransmitter in brain
 Any factor increases Glutamate activity ca...
Drugs which can cause seizures




Antibiotics
 Penicillins
 Isoniazid
 Metronidazole
Anesthetics, narcotics
 Haloth...
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...
Hypoxia



Hypoxia/anoxia markedly increase the risk of
mortality in SE
Seizures (without hypoxia) are much less dangero...
Neurogenic pulmonary edema
Rare

complication
Likely occurs as
consequence of marked
increase of pulmonary
vascular pres...
Acidosis



Respiratory
Lactic



Impaired tissue oxygenation
Increased energy expenditure
Hemodynamics


Sympathetic overdrive
 Massive
catecholamine /
autonomic
discharge
 Hypertension
 Tachycardia
 High CV...
COMMON WEALTH GAMES, DELHI 2010.
Cerebral blood flow - Cerebral O2 requirement


Hyperdynamic phase


O2 requirement



Exhaustion phase




Blood flo...
Glucose
Glucose



Hyperdynamic
phase



SE

Exhaustion phase



30 min

SE + hypoxia


Seizure duration

Hyperglyce...
Hyperpyrexia
 Hyperpyrexia may develop during protracted

SE, and aggravate possible mismatch of
cerebral metabolic requi...
Other alterations
 Blood leukocytosis

(50% of children)
 Spinal fluid leukocytosis (15% of children)

K+

creatine ki...
Boring!
Acute Management of Seizures
0-5 min
5-15 min
15-35 min

45 min
60 min
Common Sense:0-5 minutes
Stabilize the patient-

A

Oxygen, oral airway. Avoid hypoxia!

B

Consider bag-valve mask ventil...
(0-5 minutes)…
 Arterial blood gas?
 All children in SE have acidosis. It often resolves rapidly with
termination of SE
...
0-5 minutes….
 Give glucose (2-4 ml/kg D25%, infants 5 ml/kg D10%), unless

normo- or hyperglycemic
 Hyperglycemia has n...
Initial investigations(0-5 minutes)….


Labs











Na,K, Ca, Mg, PO4 , BUN, Cret, glucose
CBC
Liver function ...
Work-Up (when stable)


Lumbar puncture




CT scan/MRI scan




Always defer LP in unstable patient, but never delay...
Treatment (Pharmacotheraqpy)
5-15 minutes..
 The longer

we wait with anticonvulsant, the
more anticonvulsant we will nee...
Anticonvulsants


Rapid acting

plus


Long acting
Anticonvulsants - Rapid acting


Benzodiazepines








Lorazepam 0.05- 0.1 mg/kg i.v.(rectal dose same) upto 4-6
m...
Benzodiazepines


Lorazepam





Low lipid solubility
Action delayed 2 minutes
Anticonvulsant effect 6-12 hrs
Less re...
Anticonvulsants :15-35 minutes
(If seizures persists)


Phenytoin









15-20 mg/kg i.v. over 15-20
min
pH 12
Ext...
Anticonvulsants :(15-35 minutes)
 Phenobarbital
 15-20

mg/kg (neonate 20-30 mg/kg)i.v.
over 15-20 min
 Onset 15-30 min...
Initial choice of long acting
anticonvulsants in SE
Is patient an infant?
Is patient already receiving phenytoin?
No

At h...
If SE persists (45 minutes)







Phenobarbital if Phenytoin used
Additional phenytoin or FP 5 mg/kg (Nelson 10 mg/k...
Seizures Persists (60 minutes)
 Consider

Diazepam infusion, pentobarbital
(Barbiturate coma), midazolam, paraldehyde
or ...
Still Seizures Persists….






Induction of Barbiturate coma for 48 hrs
IV loading thiopental 2–4 mg/kg till a burst
...
Still Seizures Persists….


General anesthesia: if barbiturate coma is not
option.
 halothane and Isoflurane.
 Acts by ...
Possible new drugs for Status







Lidocaine - some positive trials
Valproate - IV form available
 10-15 mg/kg IV....
Non - convulsive status epilepticus?
 NCSE

is a term used to denote a range
of conditions in which electrographic
seizur...
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 S...
Summary
Status Epilepticus is >5 min of seizures or two seizures
without return to consciousness
 Status Epilepticus is c...
Take-Home points 






Better outcome if seizure stopped earlier, so no need to
wait
Always ABC D FIRST
Lorazepam - ...
Status epilapticus
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Status epilapticus

  1. 1. Status Epilepticus Dr. Ravindra K. Sharma Pediatric Specialist Fujairah Hospital, UAE drravindrakr@yahoo.co.in
  2. 2. TAJ MAHAL, AGRA, INDIA
  3. 3. “Status epilepticus is a medical emergency that requires an organized and skillful approach to minimize the associated mortality and morbidity”
  4. 4.  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.
  5. 5. Definition:  Conventional definition:  Single  Series seizure > 30 minutes of seizures > 30 minutes without full recovery
  6. 6. 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
  7. 7. 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
  8. 8. 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.
  9. 9. Operational Definition: “Continuous seizures lasting at least 5 minutes or two or more discrete seizures between which there is an incomplete recovery of consciousness”
  10. 10. 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 %
  11. 11. 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 
  12. 12. 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
  13. 13. Mortality   Adults Children 15 to 22% 3 to 15% Reviewed in: Fountain NB. Epilepsia 2000;41 Suppl 2:S23-30
  14. 14. Prolonged seizures Temporary systemic changes Life threatening systemic changes Duration of seizure Death
  15. 15. Respiratory  Hypoxia and hypercarbia - ventilation (chest rigidity from muscle spasm) Hypermetabolism ( O2 consumption, CO2 production) Poor handling of secretions - Neurogenic pulmonary edema? -
  16. 16. 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
  17. 17. 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
  18. 18. Acidosis   Respiratory Lactic   Impaired tissue oxygenation Increased energy expenditure
  19. 19. Hemodynamics  Sympathetic overdrive  Massive catecholamine / autonomic discharge  Hypertension  Tachycardia  High CVP 0 min 60 min  Exhaustion  Hypotension  Hypoperfusion
  20. 20. COMMON WEALTH GAMES, DELHI 2010.
  21. 21. Cerebral blood flow - Cerebral O2 requirement  Hyperdynamic phase  O2 requirement  Exhaustion phase   Blood flow  Blood pressure Seizure duration CBF meets CMRO2 CBF drops as hypotension sets in Autoregulation exhausted Neuronal damage ensues
  22. 22. Glucose Glucose  Hyperdynamic phase   SE Exhaustion phase   30 min SE + hypoxia  Seizure duration Hyperglycemia Hypoglycemia develops Hypoglycemia appears earlier in presence of hypoxia Neuronal damage ensues
  23. 23. Hyperpyrexia  Hyperpyrexia may develop during protracted SE, and aggravate possible mismatch of cerebral metabolic requirement and substrate delivery  Treat hyperpyrexia aggressively  Antipyretics, external cooling
  24. 24. Other alterations  Blood leukocytosis (50% of children)  Spinal fluid leukocytosis (15% of children)  K+  creatine kinase  Myoglobinuria
  25. 25. Boring!
  26. 26. Acute Management of Seizures 0-5 min 5-15 min 15-35 min 45 min 60 min
  27. 27. 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
  28. 28. (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
  29. 29. 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
  30. 30. 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
  31. 31. Work-Up (when stable)  Lumbar puncture   CT scan/MRI scan   Always defer LP in unstable patient, but never delay antibiotic/antiviral rx if indicated Indicated for focal seizures or deficit, history of trauma or bleeding d/o EEG
  32. 32. 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
  33. 33. Anticonvulsants  Rapid acting plus  Long acting
  34. 34. Anticonvulsants - Rapid acting  Benzodiazepines      Lorazepam 0.05- 0.1 mg/kg i.v.(rectal dose same) upto 4-6 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
  35. 35. 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
  36. 36. 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 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   
  37. 37. 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
  38. 38. Initial choice of long acting anticonvulsants in SE Is patient an infant? Is patient already receiving phenytoin? No At high risk for extravasation ? (small vein, difficult access etc.)? No Phenytoin Yes Fosphenytoin Yes Phenobarbital
  39. 39. 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
  40. 40. 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
  41. 41. 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
  42. 42. 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.
  43. 43. 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.
  44. 44. 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.
  45. 45. Non - convulsive SE ?  Up to 20 % of children with SE have non convulsive SE after tonic - clonic SE
  46. 46. 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
  47. 47. 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 
  48. 48. 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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