brief outline on management of status epilepticus in children

1. Status epilepticus

2. • Definitions
• Classifications
• Management
– pre-hospital care / out of hospital setting
– Initial stabilization
– Diagnostic tests
– Drugs for seizure control
• First line
• Second line
• Management algorithm
• Recent evidences

3. Definitions
Status epilepticus : (operational definition) (ILAE 2015)
Generalized convulsive status epilpeticus was operationally
defined as “. . .≥ 5 min of continuous seizure or two or more
discrete seizures between which there is incomplete recovery of
consciousness,”
Refractory Status epilepticus:
Clinical or EEG seizures which persist after an adequate dose of
initial benzodiazepine and a second appropriate anti-seizure
medication
Super-refractory status epilepticus:
Persistence or recurrence of seizures despite at least 24hrs of
pharmacologic coma including occurrence of breakthrough
seizures during tapering of anaesthetic medications

4. NCSE (Non-convulsive status epilepticus)
- Characterised by continuous non-motor
seizures and requires EEG confirmation for
diagnosis

5. Classification of status epilepticus
CONVULSIVE
• Generalised convulsive
• Focal motor
• Myoclonic
NON-CONVULSIVE
• Absence seizures
• Complex partial seizures
• NCSE with coma

6. Generalised convulsive status epilepticus
• 73-98% of pediatric SE
• Tonic, clonic or tonic-clonic seizure activity
involving all extremities
Focal motor status epilepticus
• Involvement of single limb or side of face
• Commonly associated with focal brain
pathology

7. Myoclonic status epilepticus
• Irregular, asynchronous, small- amplitude,
repetitive myoclonic jerking of the face or
limbs
• Commonly associated with specific conditions
or syndromes.

8. Etiological classification
ETIOLOGY DEFINITION
Cryptogenic (idiopathic) SE in the absence of an acute precipitating CNS insult or
metabolic dysfunction in a patient without a preexisting
neurologic abnormality
Remote symptomatic SE in patient with known h/o neurological insult associated
with an increased risk of seizures
Febrile SE provoked by fever in a patient without h/o afebrile
seizures
Acute symptomatic SE during acute illness involving known neurologic insult
(meningitis, TBI, hypoxia)
Progressive
encephalopathy
SE in a patient with a progressive neurologic disease

9. MANAGEMENT

10. OUT OF HOSPITAL SETTINGS
SUPPORTIVE CARE
• Stabilise
- Airway, breathing, circulation
SPECIFIC CARE
• Intravenous access not feasible?
– IM midazolam
• Intramuscular injection not feasible?
- Intranasal / buccal midazolam, rectal diazepam
• Intravenous access feasible?
– Intravenous lorazepam or midazolam

11. • Acute treatment with anticonvulsants should be
commenced after continuous seizures or serial seizures
>5 min in an out-of hospital setting
• IM Midazolam
– 0.2mg/kg (max 10mg)
• Buccal or intranasal midazolam
– as effective as rectal diazepam
– dose : 0.2 mg/kg (max 10mg)
• Rectal diazepam
– safe and effective as first-line treatment in community
setting / when intravenous access is not available.
– 0.5 mg/kg (max 20mg)

12. Initial stabilisation
AIRWAY/BREATHING
• Maintenance of an adequate airway and normal gas
exchange is a priority to avoid the consequences of
hypoxemia
• Respiratory failure can result from continuing seizures
or respiratory depression from anti-convulsants
• Supplement oxygen / support respiration
• Anticipate risk of aspiration
• Rapid sequence intubation
- in children with hypoxemia, hypoventilation,
weakened airway reflexes,
- GCS <8

13. CIRCULATION
• Reliable IV access/ IO access
• Cardiac monitoring
• Anticipate hypotension – most commonly drug induced
• Vasopressors- to maintain normal BP
• Hypertension – common with ongoing seizure activity
Rapid neurological examination and relevant history
ASSOCIATED DERANGEMENTS
• Hypoglycemia – blood sugar checked promptly and corrected (2.5ml/kg of
10% dextrose)
• Consider CNS infection – first dose antibiotic
• Prolonged seizures associated with
– Hyperthermia – treat with medications, surface/systemic cooling
– Metabolic acidosis – corrects with rehydration and cessation of
seizures
– Rhabdomyolysis -

14. STATUS EPILEPTICUS in a child without h/o seizures
FIRST LINE SECOND LINE
Random blood sugar (finger stick)
Electrolytes - Ionic calcium Sodium
If febrile - CBC
Lumbar puncture (if indicated)
MRI
EEG
Urine toxicology (if clinically suspected)
STATUS EPILEPTICUS in a known epilepsy patient
• Antiepileptic drug levels
(Rule out non-compliance/ missed dose/ recent drug or dose changes)
• If febrile - CBC, lumbar puncture
If Refractory seizures or persistent encephalopathy
• Continuous EEG monitoring
Diagnostic tests

15. DRUGS FOR SEIZURE TERMINATION
SEIZURE TYPE FIRST LINE SECOND LINE
Generalized convulsive
SE
Lorazepam Fosphenytoin
Focal motor Lorazepam Fosphenytoin
Myoclonic Lorazepam Fosphenytoin
Valproate

16. BENZODIAZEPINES
• Facilitate GABA action
LORAZEPAM
• First line treatment for all types of convulsive status
epilepticus
• Peak effect 15 minutes after dosing
• Duration 3-6 hours
• Dose : 0.1 mg/kg IV (max 4mg)
• If single dose is not effective, second dose recommended
before or concurrent with 2nd line agent
• Side effects: sedation, respiratory depression, hypotension

17. MIDAZOLAM
• Fast acting, water-soluble benzodiazepine
• Can be administered IV / IM/
Intranasal/buccal
• Rapidly absorbed via both the nasal and
buccal mucosa.
• High IM bioavailability of 90%
• Intranasal midaz may be safer and more
efficacious than rectal diazepam in
children*
• Dose
IV or IM : 0.15- 0.2 mg/kg (max 5mg)
Buccal/intranasal : 0.2 mg/kg (max 10 mg)
*McIntyre J, Robertson S, Norris E, et al. Safety and efficacy of buccal midazolam versus rectal
diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet 2005;
366:205.

18. DIAZEPAM
• Has been the drug of first choice in many settings, especially
outside the emergency department
• stable in liquid form for long periods at room temperature
• Rectal diazepam is absorbed rapidly and attains a therapeutic
level in 10 minutes.
• Less favorable pharmacokinetic profile when given IV
Dose
Rectal : 0.5mg/kg (max 10mg)
IV : 0.2-0.3 mg/kg IV (max 10mg)

19. SECOND LINE AGENTS
PHENYTOIN
• Long-acting drug that has been widely used to treat acute
and chronic seizures in children.
• Advantage is preventing recurrence of seizures for
extended periods of time.
• Because its onset of action may be delayed for 10 to 30
minutes, a rapidly acting agent, such as lorazepam, should
be given first.
• IV loading dose of 20 mg/kg, over 20 minutes (to avoid
hypotension and cardiac arrhythmias).
• An additional loading dose up to 10 mg/kg may be used in
young infants if status persists after 10 min.
• Phenytoin should be diluted only with normal saline, and
never with glucose containing solutions.

20. Fosphenytoin
• Phenytoin prodrug
• can be administered IM with rapid and complete
absorption.
• To eliminate confusion, fosphenytoin is prescribed as
milligrams of phenytoin equivalent
(a greater weight of fosphenytoin must be given in order to
yield the same concentration of phenytoin)
• Dose : 15–20 mg/kg of phenytoin equivalents/ kg, infused
at a rate of not more than 3 mg/kg/min.
• Fewer administration side effects like local irritation/
arrythmias as compared to phenytoin
• ECG monitoring recommended during administration

21. LEVETIRACETAM
• Newer anti-convulsant
• Gaining favour as 2nd line anti-convulsant
Advantages
• Rapid onset of action
• Lack of cardiorespiratory depression
• Similar bioavailability with enteral and IV dosing
Dose
• Loading dose 5-30mg/kg
• Maintainence dose 20-60 mg/kg/day

22. Drugs for refractory seizures
• Convulsive status epilepticus persisting for 30 minutes after
initial measures are instituted, further pharmacologic therapy
required in the form of continuous infusional therapy.
• PICU setting
• Midazolam infusion
– initial bolus infusion of 0.2 mg/kg IV
– followed by a continuous infusion of 0.05 to 2 mg/kg/hr
• Pentobarbital infusion
• Propofol infusion
• Lacosamide
• Topiramate

23. Focal or brief seizures
• focal seizures or brief generalized motor seizures with
relatively preserved interictal consciousness may require less
emergent intervention
• Oral or intramuscular medication can be considered
– if the seizures are not generalized convulsive or
– have stopped before the child arrives in the emergency
department
– are short in duration or
– the child is conscious despite multiple seizures.
• Oral loading with the commonly used anti-seizure drugs
reduces the risk of excessive sedation and respiratory
depression.

24. General considerations
In deciding initial therapy, the following issues
should be considered:
• Previous response— If the child has a history
of previous status epilepticus, knowing which
anti-seizure drug was effective
• Missed medication— If the child is on long-
term anti-seizure drug therapy

29. Which anticonvulsants are efficacious as initial and subsequent
therapy?
• In children, IV lorazepam and IV diazepam are
established as efficacious at stopping seizures
lasting at least 5 minutes.
• Rectal diazepam, IM midazolam, intranasal
midazolam, and buccal midazolam are probably
equally effective at stopping seizures lasting at
least 5 minutes.
• IV valproic acid has similar efficacy as IV
phenobarbital as second therapy after failure of a
benzodiazepine.

30. What adverse events are associated with anticonvulsant
administration?
• Respiratory depression is the most common clinically
significant treatment associated adverse event
associated with anticonvulsant drug treatment in
status epilepticus in children
• No difference between different benzodiazepines or
administration by any route in terms of respiratory
depression
• Adverse events, including respiratory depression
have been reported less frequently in children than
in adults

31. Which Is the Most Effective Benzodiazepine?
• No significant difference in effectiveness between IV
lorazepam and IV diazepam
• Non-IV midazolam (IM/intranasal/buccal) is probably
more effective than diazepam IV/rectal

32. Is IV Fosphenytoin More Effective Than IV
Phenytoin?
• Insufficient data regarding the comparative
efficacy of phenytoin and fosphenytoin
• Fosphenytoin is better tolerated compared
with phenytoin
• When both are available, fosphenytoin is
preferred based on tolerability

33. THANK YOU