Status Epillepticus Quick take on management and drugs

1. Status Epilepticus
HO Githushan
Ward 5A

2. Content
• Definition
• Classification
• Complications
• Guidelines
• Drugs
• Trails
• Questions

3. Definition
• GTC lasting >5 mins or occurs multiple times without regaining
normal Status in between
• Focal Seizure with impaired awareness lasting >10 mins
(NonconvulsiveSE)

4. Classification of Status Epillepticus
• Refractory Status Epilepiticus – Refractory to 1 and 2nd line Antiseizure
Meds (Benzo+Levi) – 25%
• New-onset Refractory Status Epilepticus- RSE occurring when no Hx of
seizure
• Febrile infection-related Epilepsy Syndrome
• Super-Refractory SE- Refractory to 2 antiseizure and GA tx for 24h or when
remerging during an anesthetic wean – Mostly Acute Encephalitis
• Prolonged Super-Refractory SE – Lasting >7d including need for anesthetics
• Epilepsia Partialis Coninua- ongoing Simple Focal seizure without alteration
of consciousness – not lifethreatening- lasts months or years

5. Outcomes of SE
• Short Term
• Respiratory, cardiovascular or metabolic complications and death
• Long term:
• Residual Neurologic sequale- Focal motor deficits, mental retardation,
behavioural disorders, chronic epilepsy – Epilepsia 2008
• Recurrent seizure

6. Neurology 1990

7. Guidelines

8. American Society of Epillepsy
2016

9. AAP Guidelines American
2016

10. APLS 2016

12. Best First Line Benzo
• VACoperative Trial Prospective RCT -
1998 – Does not include midazolam:
• IV Lorazepam 0.1mg/kg
The RAMPART Trial 2012:
• IM Midazolam
• “This double-blind, randomized
trial showed that prehospital
treatment with intramuscular
midazolam was at least as
effective as intravenous
lorazepam in subjects in status
epilepticus”

13. Journal Of Child Neurology – 2016 Midaz Vs
Loraz
• NonIV midazolam and IV lorazepam were superior to IV & nonIV
diazepam;
IV lorazepam was at least as effective as nonIV midazolam.
• NonIV midazolam should be recommended for the prehospital
treatment of status epilepticus in the pediatric population.
• Midazolam had the largest probability of being the best
treatment in achieving seizure cessation, and lorazepam had the
largest probability of being the best treatment in reduction of
respiratory depression.

14. Midazolam
• Rapid onset within 1 minute
• Water soluble but more lipid soluble at physiologic pH
• Use Buccolam for buccal use or draw normal Midazolam 0.5mg/kh- APLS or
0.3mg/kg (safer)–Australian
• If using IM Midazolam 0.2mg/kg use single dose and do not repeat !
• IV Midazolam 0.15mg/kg – Preferred in aussie as lorazepam in unavailable
• Short duration of action - children who stop convulsing after an initial
Midazolam dose may require a repeat dose to maintain seizure control –
Eur Journal of Pediatrics 2011

16. Principles of Treating SE
•Most seizures are self-limited.
•Often this will involve a tonic phase,followed by a clonic phase, and finally a post-ictal phase.
• If the patient is still in a tonic phase after three minutes, it is unlikely that their
seizure will break spontaneously.
•After five minutes of seizure, start aggressive benzodiazepine administration.
•Refractory status epilepticus is associated with significant mortality morbidity
•Risk of a seizure becoming refractory increases with increasing seizure
duration

17. Do not UNDERDOSE the BENZO !
• Over time, GABA receptors on neurons are internalized within cells.
This reduces the sensitivity of neurons to benzodiazepines.
• Up-front adequate dosing of benzodiazepine provides the best
chance for immediate lysis of the seizure
• IV Lorezapam 0.1mg/kg or max 4mg if >40kg
• IM Midazolam 0.2mg/kg

18. ALL STATUS Needs Prophylaxis
• In Adults – an antiseizure medication
• But in Children Fever control
• ClinicalEvidence 2013 Febrile Seizures:

19. No RCT or Systematic Review Evaluating
Physical Cooling Methods (Fan, Tepid sponging)
Studies on PCM or NSAID inconclusive if it prevents febrile
seizures or interrupts Status Epilepticus

20. Second Line Agents

21. Second Line Antiepileptics – ESETT Trial-2019

22. IV Levitracetam
• IV levitracetam 60mg/kg over 5 mins, no contraindications no
significant side effect profile
• Acts for 6-8 hours

23. IV Valproate
• Not frequently used in children due to risk of hepatotoxicity in infants
and in young children
• Avoid in children with suspected metabolic disease
• Valporate and Fosphenytoin interact so only one of these can be used
• Acts 7-13hours

24. Fosphenytoin/Phenytoin
• Traditionally first line
• Reasons not to use it:
1. Numerous drug interactions
2. Contraindications- pregnancy, hepatic or renal dysfunction –
difficult to asses in emergency (reduce dose in hepatic dysfunction)
3. Can cause severe hypotension or bradycardia if given fast- can mx
by slowing and continue medication
4. Complications- SJS, pancytopenia, phelibitis, drug fever
5. Narrow spectrum antiseizure than others (ineffective- G-myoclonic
or absence)

25. Phenytoin
• The dose is 20 mg/kg IV/IO with a rate of infusion no greater than 1
mg/kg/min. The infusion should be made up in normal
saline to a maximum concentration of 10 mg in 1 ml. Phenytoin can cause
dysrhythmias and hypotension, therefore monitor
the ECG and blood pressure (BP). It has little depressant effect on
respiration.
• Using it with dextrose can cause it to form percipitates. Less reactions
when rate <50mg/min –RCEM 2021
• Fosphenytoin is the inactive prodrug, water soluble and less local reactions
and can be infused faster. However time to Serum therapeutic levels is
same for pheny or fospheny
• Will have anticonvulsant activity for 24h

26. Phenobarbital
• 15-20mg/kg over 20 mins or at 50-100mg/min
• Respiratory depression occurs usually with >20mg/kg
• Hypotension
• Has drug to drug interactions
• Valproate reduces phenobarbital consider reducing dose by 50% -
2019 Torbey
• Consider dose reduction in hepatic dysfunction

27. RCEM 2021 and APLS 2016
• Recommends using Paraldehyde with Phenytoin or Phenobarbitone at
0.4ml/kg in equal volume oil (olive oil preferred) while preparing
phenytoin or phenobarbitone as 2nd line

28. IV Lancosamide
• 10mg/kg over 5 mins
• Minimal drug interactions
• Effective in Super RSE – Aging and disease 2021
• Half life 13 hours
• No Studies on use in children

29. Other Newer drugs
• IV propofolol – Not commonly used in children as can cause low BP
and myocardial depression
• IV Ketamine – 1-2mg/kg boluses q5mins to cumulative total 5mg/kg
• Infusion: 1-7.5mg/kg/h – titrate based on EEG
• For break through seizures rebolus with ketamine an increase infusion rate
• Target- cessation of seizures rather than burst suppression on EEG- J. Clinical
Neurology – 2021
• Preferred for superRSE
• Ketamine infusion prevented intubation – Lucrezia et Al. 2015

30. RSI
• Preoxygenation
• Induction
• Paralytic
• Note: Beware of using paralytic for intubated patients with convulsive
seizure – this makes things look nice but doesn't prevent brain
damage from the seizure
• I.e Recommended Continous vEEG monitioring

31. Preoxygenation
• Nasal Airway + NRBM + BVM until laryngoscopy

32. Induction Agent
• IV propofolol 1.5-2mg/kg + IV Ketamine 1-2mg/kg
• Synergestic effect with propofolol and ketamine
• Classically Thiopentone or propofolol was used
• In Pediatrics IV Midazolam 0.2mg/kg preffered as induction
• Resue vasopressors ! – cardiac dose Epi

33. Paralytic
• Use Succinlycholine or Rocuronium if suggamdex available
• i.e use sux – Short acting- To allow revealing physical seizure activity
to titrate sedating agents
• ROC preferred if fits >20 mins as sux risk of HyperK
• IV Succinly chloride 1-2mg/kg
• Or IV Rocuronium 0.6-1.2 mg/kg

34. After intubation

35. Pharmacological Coma – low evidence
• Preferred agents
• 1st line IV midazolam infusion
• 2nd line IV phenobarbital

36. Additional Therapies

37. Weaning off
• O. Clobazam can be considered while weaning off IV drugs

38. RSI + Sedation + Antiepileptics
First !
If not sure of length or presenting with seizure >30mins

39. On Going Studies
• EEG monitoring for RSE – UK NHS 2022-2023
• Efficacy of IV Levitracetam vs IV Phenytoin in children –Lahore
Pakistan (King Edward medical university)

40. • A 3 wo infant presents to the ED for abnormal facial twitching. During
your exam, he begins to have facial and mouth twitching on the left
followed by arm and leg movements, and then generalized tonic-clonic
convulsions. You obtain IV access and determine that the glucose, sodium
and ionized calcium levels are normal. After supporting the ABCs, which
of the following is the most appropriate approach in management for this
actively convulsing patient?
1. Aggressively treat any witnessed seizure activity with anticonvulsants
2. Administer half the normal pediatric anticonvulsant loading dose
3. Administer phenobarbital until generalized convulsions stop; observe focal facial twitching
closely
4. Observe the patient until generalized convulsions exceed 5 minutes in duration, then treat with
anticonvulsants
5. Admit for video EEG, and determine appropriate anticonvulsant therapy once the EEG is
reviewed

41. • Answer 1
• Aggressively treat any witnessed seizure activity with anticonvulsants in neonates:
• Neonates are at high risk for seizures also more likely to have significant apnea with
seizures, or to have subclinical seizures.
• Unlike seizures in older children, brief focal neonatal seizures can affect brain
development and alter neuronal circuitry, resulting in impaired memory and learning.
• Neonates are more likely to have subclinical seizures for a period of time before the
seizures become more clinically apparent.
• Phenobarbital as first-line for neonatal seizure; however, phenobarbital and phenytoin
are equally efficacious.
• If seizures persist after first-line anticonvulsant therapy, a trial of pyridoxine (vitamin B6)
or folic acid pending metabolic studies should be considered.
• There is no role for withholding anticonvulsant therapy while a neonate is seizing, or for administering ½
the pediatric loading dose. Focal seizure activity should be as aggressively treated as generalized
convulsions. While a Neurology consult and video EEG monitoring for neonatal seizures may be indicated,
withholding anticonvulsants prior to EEG is not recommended.

43. Thank you