Status-Epilepticus-2nd-part-Final-Dr-Mamun(1).ppt

Epilepsy in children

1. Dr.Md Mamun Sarker
DCH Student
2
nd
Year
ICMH, Dhaka,
05/02/2024

3. Introduction & Definitions
Causes
Investigation
Evidence-Based treatment options
Algorithm
Conclusion
Objectives

4. Introduction
Status Epilepticus(SE) is a common neurological
emergency with a higherrate of mortality,
neurodevelopental sequelaeand morbidity.
SE may occur as a first presentation of a seizure
disorder in the life span of epilepsy or neurologically
ill patient or due to infection ,trauma , hypoxia, or
metabolic causes.

5. Definition
Definition of SE to reflect the time at which
treatment should be initiated (t1)
Time at which continous seizure activity leads to
long term sequelae such as neuronal injury (t2) .

6. Definition con’t
The 5 mins window corresponds with the time at which
urgent treatment should begin.
The classical 30 mins cut off is based on the fact that
approximately after 30 mins of generalized seizures, the
compensatory mechanisms fails against acidosis,
hyperthermia ,hyperkalemia , and cardiocirculatory
collapse .
Thus SE induced irreversible neuronal damage occures and
seizures become self-sustained and refractory to treatment.

8. Definition:
Historically, status epilepticushas been conceptually
defined as “A condition characterized by an epileptic
seizure that is sufficiently prolonged or repeated at
sufficiently brief intervals so as to produce an unvarying
and enduring epileptic condition” . Roger J 1974
The International League Against Epilepsy: 30 min of
continuous seizure activity, or a series of epileptic seizures
during which function is not regained between ictalevents
in a longer than 30 min period. Epilepsia. 1993

9. Epidemiology
Approximatley17-23 of 100,000 children
experience SE every year.
From neonate to 1 year of age: 135–150 incidents
per 100,000 children
Between age 1-4 yrs(29 of 100,000)children,
Aged 5-9 yrs(9 of 100,000) children,
And aged 10-15 yrs(2 of 100,000) children
Mortality at 3%

10. Incidence
The incidence is highest in the neonatal period
Approximately 30% of patients presenting with SE
are having their first seizure and approximately
40% of these later develop epilepsy .

11. Classification
SE may be subclassifiedas
oConvulsive: generalized tonic-clonicmovements,
mental-status impairment, postictal focal neurologic
impairment. 90%of all SE.
oNonconvulsive: wandering confused, mental status
impairment with or without motor movements.
oRefractory: not responsive to standard treatment. It
is defined as clinical or electrographic seizures that
continue despite adequate benzodiazepine doses and
at least one acceptable antiepileptic drug (AED).
Occurs in 30% SE.

13. Causes
of SE

14. Causes of SE Con’t
Known (symptomatic):
oAcute (stroke, toxicity, derangements in serum electrolytes
and blood glucose, trauma,hypoxia, febrile seizures,
neuroinfections, and inborn errors of metabolism)
oRemote (brain scars due to above causes, genetic, brain
malformations, etc.)
oProgressive (neurodegenerative disorders and tumors)
oKnown cases of epilepsy: Lennox–Gastaut syndrome and
Dravet syndrome
Unknown cause: new-onset refractory status epilepticus
(NORSE), febrile infection-related epilepsy syndrome
(FIRES)

15. Mechanisms:
The establishment of sustained seizure activity seen in
SE appear to involve:
1) Failure of desensitization of AMPA (Alpha
amino -3-hydroxy-5-methyl-4-isoxazolepropionic acid)
glutamate receptors, thus causing the persistence of
increased excitability
(2) Reduction of GABA-mediated inhibition as
a result of intracellular internalization of GABA-A
receptors.

16. Pathogenesis

17. Pathogenesis
Failure of the normal mechanisms that terminate seizures
Reduced inhibitionand persistent excessive
excitation ,Ongoing seizure activity ↓GABA receptors
Pronounced excitation via glutamate analogues leads
to prolongation of seizures

18. Mechanism Con’t
During SE, there is an increased cerebral metabolic
rate and a compensatory increase in cerebral blood
flow.
When the brain is exposed to prolonged seizures ,
there is a rapid decrease in number of post synaptic
GABA-A and increase in the number of post synaptic
NMDA receptors .
This loss of inhibition and increase in excitation in the
brain synapses promote self sustaining prolonged
seizure and may explain the loss of efficacy of
benzodiazepines

19. Management
History taking, investigation and treatment go
simultaneously
Status epilepticus is a medical as well as neurologic
emergency

20. In children with new-onset seizures, after
continuously seizing for 5–10 min, a seizure
becomes unlikely to stop without pharmacologic
intervention
Several studies have described associations
between status epilepticus management delays
and more prolonged seizures and lower anti-
seizure medication responsiveness
Thus we have to start treatment as early as possible

21. Quick History
Elicit quick history
Trauma
Antecedent illness
Fever
Ingestion
Skipped medication

22. Management con’t
Ideal drug for treating SE
Rapid entry into CNS
Rapid onset of action
Long duration of action
Safety
Absence of sedation
Useful as maintenance AED

23. Management Con’t:
Stage 1: Early phase (duration from 5 to 10 minutes)
ABCDE
Maintain Airway-patient at risk for aspiration
Breathing-place O
2, be ready for intubation
Circulation-obtain IV access
Dextrose: check glucose levels
Electrolytes: check electrolytes (Na, Ca, Mg, PO
4)
Check anticonvulsant levels

24. Investigations
CBC
Serum electrolytes ,ABG
Ca, Mg, PO
4
Glucose
Liver function tests, S/ Creatinin
S/ Ammonia, Lactate
Anticonvulsant levels
Toxic screen
cEEG
Neuroimaging: CT Scan of Brain (use contrast if suspect brain tumor or
AVM)

25. Investigation Con’t
Lumbar puncture
Always defer LP in unstable patient, but never delay
antibiotic/antiviral rx if indicated
CT scan
Indicated for focal seizures or deficit, history of trauma
or bleeding

27. Treatment
Stage 1
Benzodiazepine Therapy
Diazepam
Lorazepam
Midazolam

28. Studyofout-of-hospitaltreatmentofseizures
lorazepamvsdiazepam.
Seizureactivityterminatedin
60%ofthelorazepam-treatedpatients
43%ofdiazepam-treatedpatients
21%ofpatientswhoreceivedplacebo
Benzodiazepines
AlldredgeB.K.,Gelb A.M.,Isaacs S.M.,et al:Acomparison of lorazepam,
diazepam, and placebo for the treatment of out-of-hospital status
epilepticus. NEnglJ Med345.(9): 631-637.2001;
Status Epilepticus Treatment

29. Diazepam
Highly lipid soluble
Rapid CNS entry-stops seizures in 1-3 minutes
Rapid redistribution in fatty tissues
Brain concentrations fall quickly
Duration of action is 15-30 minutes
T1/2= 30 hr
Dose: <3yrs, 0.5mg/kg, >3yrs, 0.3mg/kg
Side Effects: sedation, decreased respiration and
blood pressure

30. Lorazepam
Less lipid soluble than diazepam
Slower CNS, stops seizures in 6-10 min
Not as rapidly redistributed to fat stores
Longer duration of action 12-24 hr
T1/2 =14 hr
Dose: 0.05—0.1mg/kg
Side Effects: decreased LOC, respiration and BP

31. Midazolam
Midazolam
(buccal/nasal)—2
puffs/5 kg weight (0.1–
0.2 mg/kg/dose)
Buccal midazolam (0.5
mg/kg)

32. Benzodiazepines lose effectiveness in established
SE and are suboptimal for long time anti-seizure
management; therefore next line AED should be
ordered and administered early, within 10 min of
seizure onset.

33. When to start 2
nd
line Anticonvulsant
Ifseizurescontinuefor10minutesafteratleast
twoinjectionsofabenzodiazepine,asecond
therapywithalong-actingantiseizuremedication
shouldbegiven(oneguideline)
Antiepilepticdrugsshouldbeadministered
concurrentlywithbenzodiazepines(one
guideline)

34. STAGE II: Established Status Epilepticus
(duration from 10 to 30 minutes)
The American Epilepsy Society’s guideline concludes that
There was insufficient evidence to evaluate phenytoinor
levetiracetamas second-line therapy (level U evidence)
I/V valproicacid has similar efficacy but better tolerability
than intravenous phenobarbital (level B evidence)

35. Comparison
Phenytoin
IV dosing 20 mg/kg load
•Onset 10-30 min
1mg/kg/min
Extravasationcauses severe
tissue injury
May cause hypotension,
dysrhythmia
Precipitates with Glucose
containing fluid
Can not be given in renal
insufficiency,
hypoalbuminemia
Fosphenytoin
IV dosing 20 mg/kg load
•Onset 5-10 min
1.5mg/kg/min
Extravasationwell tolerated
May cause hypotension

36. STAGE III: Refractory Status Epilepticus
(Refractory GCSE)(duration from 30 to 60
minutes)
The definition of refractory generalized CSE (GCSE) is
based on the number of anticonvulsants used
A patient is considered to have refractory SE when
Seizures continue despite first-and second-line
treatments and the seizures duration is greater than 1 hour
there is a need for general anesthesia

37. Refractory Status Epilepticus
Intubation
Continuous EEG monitoring
Drugs: Levetiracetum. Phenobarbiton, Sodium Valproate
Medication Coma
Pentobarbital
Midazolam
Propofol
Very high dose phenobarbiton

38. Treatment Stage III
Phenobarbiton
Lipid solubility < Phenytoin
Duration of action>48 hrs, T1/2= 100 hours
Dose : 15–20 mg/kg IV, may give an additional 5–10 mg/kg
Side Effects: sedation, decreased respiration and BP

39. Management of refractory status epilepticus
General anesthetics to achieve burst suppression
Midazolam—0.2 mg/kg IV bolus followed by infusion @1
μg/kg/ min, increasing 1 μg/kg/min, every 5–10 minutes,
till seizures stop, up to a maximum of 30 μg/kg/min,
tapering initiated after 24 hours of seizure control @ 1
μg/kg/min, every 3 hours

40. High-dose phenobarbitone: 5–10 mg/kg boluses every
30 minutes up to 120 mg/kg over 24 hours, target seizure
control and burst suppression, maintenance up to 40
mg/kg/day
Propofol:loading dose of 1–2 mg/kg, followed by
continuous infusion of 1–2 mg/kg/h, maximum of 5
mg/kg/h. Propofol infusion should not be used in
children due to the risk of propofol infusion
syndrome).
Thiopentone:loading dose 5 mg/kg bolus followed by 3–
5 mg/ kg/h infusion rate to achieve burst suppression
followed by tapering after 24 hours seizure free period.

41. Topiramatethrough orogastric/nasogastric tube (2–5
mg/kg enteral loading, increase by 5–10 mg/kg/day up to
maximum of 25 mg/kg/day) while tapering anesthetic
agents.
Ketaminecan also be tried.

42. Levetiracetum
Consider LevetiracetumIV Loading
High bioavailability
Few drug interaction
Low plasma protein binding
Minimal hepatic metabolism
•Can be considered second-line
•May be preferred over benzodiazepines in specific
patients with respiratory compromise and/or
hypotension
Dose: 20-60 mg/kg

43. Valproate
Consider IV Valproic Acid
FDA approved only for replacement or oral dosing
Rapid loading dose appears safe
25-30mg/kg rapidly infused
Side Effects: dizziness, nausea
Can be initial therapy in patients with increased risk of
cardiac or respiratory abnormalities
Concern for hepatotoxicity with valproic acid use in
children younger thantwo years).

44. Stage IV: Super refractory status epilepticus
(duration > 24 hours)
When treatment with an IV anesthetic for more than 24 h
is not successful in controlling SE, the condition can be
termed superrefractory SE or malignant SE.
The first line therapy includes maintaining the use of
anesthetic drugs used in Phase III although other drugs
have been reported with uncertain outcomes such as
Ketamine
enteral topiramate
perampanel
bumetanide

45. Other therapeutic options included :
Hypothermia
Magnesium Infusion
Pyridoxine Infusion
KetogenicDiet
Immunologic Therapy ( InjMethyl Prednisolone,
IVIG)
Emergency neurosurgery including
focal resection, multiple subpialtransection,
corpus callosotomy, and hemispherectomy

46. Some recommendations
When I/V access is not possible I/M fosphenytoin
( 18-20 mg/kg) can be given as a single dose
Children already getting oral phenytoin should be
cautiously given inj phenytoin @ 5 mg/kg over 5 min and
wait for blood phenytoin level

47. If the patient progresses to refractory status
epilepticus, urgent escalation of therapy should be
continued
At this point, options include administering
another bolus of the same second-line agent that
had been given or adding another agent from the
ones just discussed.
Status Epilepticusin Adults: A Review of Diagnosis
and Treatment.2016

48. Supportive Therapy
Glucose Infusion: 10% dextrose 2ml/kg
Hyperglycemia has no negative effect in SE
(as long as significant hyperosmolalityis being
avoided)

49. Supportive Therapy
Inj Mannitol 5ml/kg over 10 min if seizure
continues for 30 min to decrease cerebral oedema
In any step if seizure is controlled, start on
maintenance therapy-after 12hours of bolus dose
Maintenance dose of Phenobarbintone–2.5-4
mg/kg/dose 12 hourly and in case of Fosphenytoin
it is 7.5mg/kg/dose 12 hourly.

50. Tapering
In Pt having continuous infusion of an AED-after
cessation of seizure, the infusion should be
continued for 12-24 hours. Then gradual tapering
is advised over 24 hour

59. Outcome and prognosis
Factors that determine outcome include
Age of the child
Rapidity of seizurecontrol
Adequacy of care
Time from seizureonset to initiation of treatment
is inversely corelated with the % of patient who
responded to 1st line AEDs.
-at 30 mins 80% responded
-at 90 mins 44%
Periodic lateralized epileptiform discharges at any
time of SE , associated with poor outcome.

60. Neurologic sequelae
Focal motor deficit
Intelluctual disability
Behavioral disorders
Epilepsy
Learning disorder

61. Take Home Message
Status epilepticusis a medical emergency
Better outcome if seizure stopped earlier
Early treatment and stepwise treatment is the
most important prognostic factors
Consideration of NCSE should be kept in mind
Targeted investigations should be done
Supportive management is very important
Planning should be done to prevent further attacks