Status Epilapticus

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

13. Prolonged seizures
Temporary
systemic
changes
Life
threatening
systemic
changes
Duration of seizure
Death

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

23. Acute Management of Seizures

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

30. Anticonvulsants
• Rapid acting
plus
• Long acting

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