convulsive status epilepticus- treatment- dr mohamed i abunada

1. Pediatric Status Epilepticus
Dr Abunada Mohamed

2. Status Epilepticus
 Status Epilepticus is a neurologic emergency
associated with high mortality and long-term disability
– Adverse consequences can include hypoxia,
hypotension, acidosis and hyperthermia
– Know the recommended sequential protocol for
treatment with benzodiazepines, phenytoin, and
barbiturates.
– Goal: stop seizures as soon as possible

3. Epidemiology
• The annual incidence of SE in children is reported
as 10 to 73 episodes/100,000 children and is
highest (135/100,000 to 156/100,000 children) in
children younger than two years of age.
• Mortality has been reported to be between 2.7%
and 8%, with an overall morbidity of between
10% and 20%

4. Definition
• SE was defined as a seizure lasting longer than
30 minutes or a series of seizures without a
return to baseline level of alertness between
the seizures.
• There is increasing recognition that most
seizures are brief (3-4 minutes) and medication
administration delay is associated with more
refractory seizures.

5. • This has led to a change in clinical practice that
has shortened the seizure duration of SE over
the last decade to a seizure lasting longer than
5 minutes.
• Recent commentaries have proposed that
aggressive management be initiated even
earlier than 5 minutes.

6. The longer SE persists,
 the lower is the likelihood of spontaneous
cessation
 the harder it is to control
 the higher is the risk of morbidity and
mortality
Bleck TP. Epilepsia 1999;40(1):S64-6
The Status Epilepticus Working Party. Arch Dis Child 2000;83(5):415-9.

7. Based on timing
SE may be categorized based on etiology, seizure type, or
timing.
 Attention to the timing stage of SE ensures management
proceeds without delay.
 In the initial 5 minutes of seizure, a period referred to as the
prodromal stage, it is unknown whether the seizure will self-
terminate or evolve into SE.
Persisting SE may be divided into
early SE ‘impending’ (5-30 minutes),
established SE (30 minutes), or
Refractory SE (RSE) (seizures that persist despite
treatment with adequate doses of an initial 2 or 3
anticonvulsant medications).

8. Based on seizure type
SE can be classified based seizure type into
 Generalized Convulsive Status Epilepticus
(GCSE) ,the most easily recognizable form
 Non - convulsive status epilepticus (NCSE) on
the basis of both clinical and electrographic
criteria.

9. Common etiologies of pediatric CSE
 Prolonged febrile convulsion (23% to 30%)
 Acute symptomatic (17% to 52%)
– Acute CNS infection (bacterial meningitis, viral meningitis or
encephalitis)
– Metabolic derangement (hypoglycemia, hyperglycemia, hyponatremia,
hypocalcemia or anoxic injury)
– Antiepileptic drug noncompliance or withdrawal
– Non-antiepileptic drug overdose
 Remote (16% to 39%)
- Cerebral migrational disorders (lissencephaly or schizencephaly)
- Cerebral dysgenesis
- Perinatal hypoxic-ischemic encephalopathy
- Progressive neurodegenerative disorders
 Idiopathic/cryptogenic (5% to 19%)

10. Status epilepticus
Drugs which can cause seizures
Antibiotics
Penicillin's
Isoniazid
Metronidazole
Anesthetics, narcotics
Halothane, enflurane
Cocaine, fentanyl
Ketamine
Psychopharmaceuticals
Antihistamines
Antidepressants
Antipsychotics
Tricyclic antidepressants

11. Status epilepticus
Prolonged seizures
Duration of seizure
Life
threatening
systemic
changes
Death
Temporary
systemic
changes

12. Pathophysiology
• Status Epilepticus results from a combination of persistent cellular
excitation and a failure of centrally mediated mechanisms to
suppress sustained seizure activity
• Generalized SE is also associated with several systemic physiologic
changes as a result of a massive release of catecholamines.
• Early manifestations (during the first 30 minutes of SE) include
 Cardiac arrhythmia
 Hyperglycemia
 Hypertension
 Lactic acidosis
 Tachycardia.
• Just beyond 30 minutes, blood pressure and glucose concentration
may begin to normalize, or even reverse in abnormality.

13. Prolonged SE (beyond 60 minutes) may be associated with
Hyperthermia,
Hypoglycemia,
Hypotension,
Pulmonary edema,
Renal failure
Rhabdomyolysis.
Cerebral ischemia from hypoperfusion

15. Imaging Evidence of SE Damage

16. The objectives for the acute management
of CSE are as follows:
1. Maintenance of adequate airway, breathing and
circulation (ABCs).
2. Termination of the seizure and prevention of
recurrence.
3. Diagnosis and initial therapy of life-threatening
causes of SE (eg, hypoglycemia, meningitis and
cerebral space-occupying lesions).
4. Management of refractory status Epilepticus
(RSE).

17. 1. Maintenance of adequate ABCS
• Inability to maintain the airway is the most
important immediate risk to the patient
with CSE.
• Factors responsible for the airway and ventilation
being at risk include
a clenched jaw,
poorly coordinated respirations, and
production of secretions and vomitus.
• Management of the airway includes
positioning the child on the side
suctioning the easily accessible secretions.

18. • After suctioning, the patient should be repositioned
on the back and a chin lift or jaw thrust should be
applied, if necessary, to help open the airway.
Hypoxia is frequently present.
• Oxygen (100%) should be given by face mask, and
cardiorespiratory and oxygen saturation monitors
should be used.
• Breathing should be carefully monitored.
• Assisted ventilation should be considered if signs of
respiratory depression or if oxygen saturations
remain low despite receiving 100% oxygen by face
mask.

19. • Increased heart rate and blood pressure (BP) are
usually observed in the convulsing patient.
Bradycardia, hypotension and poor perfusion are
ominous signs.
They imply severe hypoxia and an immediate need to
establish the airway and ventilate the patient, either
by bag-valve mask ventilation or intubation.
• Intravenous (IV) access should be obtained
immediately (two large-bore IV lines if possible)
and the bedside blood glucose level should be
checked.
Further testing should be considered once the ABCs
have been stabilized.

20. 2. Termination of the seizure and
prevention of recurrence
 The major goal of treatment is to stop the seizure and
prevent brain injury.
 In animal models, ischemic and excitotoxic neuronal
cell loss starts to occur after 30 min of seizure activity.
 Seizures that last longer than 5 min to 10 min are at
high risk of continuing for at least 30 min, so early
treatment is associated with the best outcome.
This is the rationale behind assuming that any child who
arrives in the ED with acute GTC convulsions is in early SE,
which should immediately trigger the first-line treatment
with benzodiazepines.

21. IV access
• If IV access is unavailable, then other routes
(eg, buccal, intranasal and rectal) should be
used while efforts to establish access continue.
• Consideration should be given to starting an
intraosseous (IO) line if IV access is not possible
and the seizure is prolonged or the patient is
decompensating.

22. Important to obtain a brief history
• It is important to obtain a brief history including
any history of seizure disorder, other symptoms
(eg, fever), medication usage and allergies to
medications.
• This can be completed by a designated person not
immediately involved in the acute resuscitation.
• This history will allow a simultaneous search for
cause and focused physical examination to be
completed while termination of the seizure is
undertaken.

23. Bedside glucose determination
• A bedside glucose determination will establish the
need for a bolus of dextrose.
• If the blood glucose level is 2.6 mmol/L or lower,
then the recommended management is 5 mL/kg of
10% dextrose water (0.5 g/kg) by IV.
• If the patient is hypoglycemic, the bedside glucose
level should be rechecked 3 min to 5 min post
bolus, and a repeat bolus should be given as
necessary.
• Increased intracranial pressure (ICP) or sepsis
should be suspected and treated as needed.

24. • During the administration of medications, pulse
rate, respiratory rate, BP, cardiac monitoring and
oxygen saturation via pulse oximeter should be
followed on a regular basis.
• Anticonvulsant medications may cause loss of
airway reflexes, respiratory depression,
hypotension and cardiac arrhythmias.
• Monitor the child’s temperature and aim for
normothermia using acetaminophen and
ibuprofen as appropriate.

25. First-line treatment
First-line treatment usually begins outside the hospital.
It has been shown that prehospital treatment of
children reduces seizure length but often is not
utilized.
Benzodiazepines are the first-line drugs of choice in
the treatment of SE.
If used within the first 20 min of seizure onset,
termination rates of seizures can be as high as 70% to
85%.
Because IV administration results in more rapid onset
of action and improved bioavailability and efficacy, IV
access should be obtained as soon as possible.

26. Status epilepticus
The longer you wait to administer anticonvulsants, the
more anticonvulsants you will need to stop SE
Most common mistake is ineffective dose.
Alternative routes of administration .
If IV access is delayed or impossible, many AEDs can be
given by alternative routes, such as rectal , buccal
or interosseous administration.
Intranasal midazolam is effective, and i.m. fosphenytoin
are safe, well tolerated, and absorbed quickly.

27. 29Status epilepticus
Anticonvulsants - Rapid acting
• Benzodiazepines
– Lorazepam 0.1 mg/kg i.v. over 1-2 minutes
– Diazepam 0.2 mg/kg i.v. over 1-2 minutes
– If SE persists, repeat every 5-10 minutes

28. Status epilepticus
Benzodiazepines
• Diazepam
– High lipid solubility
– Thus very rapid onset
– Thus rapid loss of
anticonvulsant effect
– Adverse effects are
persistent:
• Hypotension
• Respiratory depression
• Lorazepam
– Low lipid solubility
– Action delayed 2 minutes
– Anticonvulsant effect 6-12 hrs
– Less respiratory depression
than diazepam
• Midazolam
– May be given i.m.

29. Status epilepticus
Benzodiazepine - Rectal
• Rectal diazepam
– 0.3 to 0.5 mg/kg rectal gel, typically reaches
anticonvulsant levels within 5-10 minutes
– Intravenous solution given rectally is equally effective
(and much cheaper)
Seigler RS. J Emerg Med1990;8(2):155-9.
– Cost :
• 5 mg Diastat rectal gel Shekel 38.00
• 5 mg diazepam intravenous solution Shekel 4.00

30. Status epilepticus
Benzodiazepine - Intramuscular
• Intramuscular midazolam
– 0.2 mg/kg i.m.
– Aqueous solution is rapidly absorbed,
anticonvulsant effect begins after 2 minutes
• Intramuscular lorazepam
– Can be given, but lacks water solubility, thus later
onset than midazolam
Chamberlain JM. Pediatr Emerg Care 1997;13(2):92-4.
Towne AR. J Emerg Med 1999;17(2):323-8.

31. Prehospital
• Treatment varies depending on local practices
and availability, but options include the
following:
Buccal or rectal lorazepam;
Buccal or intranasal midazolam
Rectal diazepam.
• If available, some would consider buccal or
intranasal midazolam to be the first-line
management in children without IV access.

32. In hospital:
• IV lorazepam is usually the first-line
treatment.
It has a longer-lasting anticonvulsant activity
causes less respiratory depression than diazepam ,
more effective than diazepam or phenytoin in
stopping seizures .
• Note that repeat doses are much less likely to be
effective (17% versus 85% for the first dose).
• If children have received benzodiazepines in the
prehospital setting, one repeat IV dose may be
adequate before moving to second line treatments
if necessary.

33. NO IV LINE
Because timing is critically important, if no IV
access is available, a second dose of
benzodiazepine (lorazepam, midazolam or
diazepam) should be given through the buccal,
intranasal, rectal or intramuscular (IM) route
while IV access is being obtained.
• Treatment with more than two doses of
benzodiazepines is associated with respiratory
depression.

34. Second-line treatment
• Fosphenytoin/phenytoin is generally preferred
over phenobarbital because it is less likely
to cause respiratory depression
to alter the level of consciousness of the child,
which can complicate the assessment.
• If no IV access is available, then IM fosphenytoin,
IO phenytoin are alternative options.
• Note that evidence for the safety and efficacy of
IO phenytoin or phenobarbital is scant.

35. Phenytoin and fosphenytoin:
• Phenytoin has been shown to control 60% to 80% of seizures with a 20 mg/kg
dose .
• It must be administered in normal saline (NS) because it precipitates in
glucose-containing solutions.
• It is infused over approximately 20 min.
• Because of its high pH, extravasation of phenytoin can result in severe
subcutaneous irritation (‘purple glove syndrome’) characterized by edema,
discolouration and pain distal to the site of administration.
• This side effect does not occur with fosphenytoin (20 mg/kg/dose), which is
 a water-soluble prodrug of phenytoin.
 more rapid IV infusion
 may be given by IM injection,
 but more expensive
 not universally available
• Side effects of both phenytoin and fosphenytoin include cardiac arrhythmias,
bradycardia and hypotension, so continuous BP and ECG monitoring is
recommended during infusion.

36. Status epilepticus
Anticonvulsants - Long acting
• Phenytoin
– 20 mg/kg i.v. over 20 min
– pH 12
Extravasation causes
severe tissue injury
– Onset 10-30 min
– May cause hypotension,
dysrhythmia
– Cheap
• Fosphenytoin
– 20 mg PE/kg i.v. over 5-7 min
PE = phenytoin equivalent
– pH 8.6
Extravasation well
tolerated
– Onset 5-10 min
– May cause hypotension
– Expensive

37. Phenobarbital:
• Phenobarbital has similar anticonvulsant activity as
phenytoin, but a greater incidence of respiratory depression,
especially when used in conjunction with benzodiazepines.
• The mechanism of action is similar to benzodiazepines, so it
may be less effective in treating seizures refractory to these
drugs.
• It is still routinely used for the treatment of neonatal
seizures, as well as for children who are already on
phenytoin maintenance.
• The loading dose is 20 mg/kg in NS or 5% dextrose water
over 20 min.
• Side effects include sedation, respiratory depression and
hypotension, especially if a benzodiazepine has already
been given.

38. 3. Diagnosis and initial therapy of life
threatening causes of SE
• Investigations should be individualized according to
the clinical scenario
• The most common cause of SE is a prolonged febrile
seizure.
• The same may apply to children with a known seizure
disorder who are already on anticonvulsant therapy.
However, a full clinical assessment should involve a
search for precipitating causes, focusing on signs of
infection, meningeal irritation, trauma, focal
neurological deficits and intoxication.

39. Investigations
• When the etiology of the seizure is unclear, the
following investigations should be considered :
 glucose (to verify earlier bedside determination)
 Electrolytes, Serum calcium
 CBC and differential
 cultures (if sepsis is suspected)
 arterial blood gas (ABG)
 Anticonvulsant levels (for patients on long-term
anticonvulsant therapy)
 Urine and blood for toxicology screening, blood urea
nitrogen, magnesium, liver enzymes, lactate and
ammonia may be required in selected cases.

40. lumbar puncture (LP)
• A decision regarding the need for (LP) should
be deferred until
the patient’s vital signs are stable
there is no suspicion of increased ICP and
the convulsion has stopped.
• If sepsis is believed to be likely, IV antibiotics
may be given immediately after blood cultures
without waiting to perform the LP.
• Prolonged attempts at obtaining cultures
should not delay treatment.

41. Computed tomography (CT) of the head
• Head CT may be performed after the ABCs have been
stabilized and the convulsion has terminated
(CT) head Indications
 A history of trauma,
 Evidence of increased ICP
 Focal neurological signs
 Unexplained loss of consciousness or
 Suspicion of cerebral herniation
• If there are clinical indications of raised intracranial pressure or
herniation, these must be treated immediately before further
investigation.
• A normal CT scan does not exclude significantly increased ICP.
• LP must be deferred if clinical or radiological signs of
increased ICP are present.

42. 4. Management of RSE
• SE that is unresponsive to two different
antiepileptic medications (eg, a benzodiazepine
and phenytoin) is considered to be refractory,
although some authorities have added a duration
criterion such as longer than 30 min or longer
than 60 min .
• Escalation to anesthetic support with subspecialist
and intensive care consultation and initiation of a
midazolam infusion

43. • It is recognized that paralysis may aid
ventilation and prevent the motor
manifestations of seizures, but it does not
terminate the seizure activity in the brain.
• At this point, the patient’s care is beyond the
scope of the usual emergency department
setting, and transfer to a paediatric intensive care
unit with neurological consultation for further
management will be necessary.

44. Pharmacotherapy in RSE
• There are currently no published controlled trials
examining different treatment options for RSE in
children.
• A number of Canadian hospital guidelines have
incorporated a continuous infusion of midazolam
as the first step.
• If this fails, then anesthetizing doses of
barbiturates should be considered.
• Most recently, the use of topiramate and
levetiracetam has been suggested, but the role of
these drugs remains unclear at the present time.

45. 47Status epilepticus
Non - convulsive status epilepticus
• How do you tell that patient’s seizures have
stopped?

46. Status epilepticus
Non - convulsive SE ?
• Up to 20% of children with SE have non -
convulsive SE after tonic - clonic SE
• Particularly common in infants < 2 months
Mitchell WG. J Child Neurol 2002;17 Suppl 1:S36-43.

47. 49Status epilepticus
Non - convulsive SE ?
• If child does not begin to respond to painful
stimuli within 20 - 30 minutes after tonic -
clonic SE stops, suspect non - convulsive SE
– Urgent EEG

48. Conclusion
• There have been a number of changes in the
emergency management of SE over the past
15 years based on the emergence of new
evidence and medications.
• It is important for all those involved in the
acute medical management of children to
have an up-to-date, evidence-based approach
to the emergency management of children
with CSE.

49. GUIDELINE FOR THE MANAGEMENT OF CONVULSIVE STATUS
EPILEPTICUS IN PEDIATRICS
yes no
noyes
- IV/I0 phenytoin 20 mg/kg in NIV phenobarbital 20 mg/kg over 20min
Is child on
phenytoin?
Insert intraosseous (IO) needle
if seizure is not stopped with
rectal benzodiazepines.
Buccal midazolam 0.5 mg/kg (max 10mg)
Or
Intranasal midazolam 0.2 mg/kg (max 10 mg)
Or
Rectal diazepam 0.5 mg/kg/ (max 10 mg)
Benzodiazepine can be repeated once
after 5 min
- IV diazepam 0.3 mg/kg over 2
min (max 5 mg in infants and 10 mg
in child)
Benzodiazepine can be repeated
once after 5 min
IV attempts should be limited to 3
tries or 90 seconds
CONVULSION > 5 MIN
Manage ABCs
1.Cardiac monitor; oximeter
2.Establish IV access
3.Place in the recovery position
Blood tests
4.CBC, electrolytes and glucose; glucometer
5.Measure blood level if on Phenobarbital, Phenytoin, Carbamazepine or
Valproate.
Rapid IV
access
obtained?