1. Convulsive Status epilepticus
Dr. Jithangi Wanigasinghe
Senior Lecturer
Consultant Paediatric Neurologist MPhil, MD, DCH

2. Scope What is CSE in the ED? What are we dealing with? What do we do?
Operational definition and new definition
What are we dealing with?
Underlying aetiology
What do we do?
Optimal management

3. Definition
Single seizure lasting more than 30-min duration or a series of epileptic seizures during which function is not regained between ictal events in a 30-min period Commission of Epidemiology and prognosis ILAE 1993

4. Operational definition for management of SE
Generalized, convulsive status epilepticus in adults and older children refers to a 5 min of (a) continuous seizures or (b) two or more discrete seizures between which there is incomplete recovery of consciousness Lowenstein D H 1999

5. New definition of CSE
Status epilepticus is a condition resulting either from the failure of the mechanisms responsible for seizure termination or from the initiation of mechanisms, which lead to abnormally, prolonged seizures (after time point t1). It is a condition, which can have long-term consequences (after time point t2), including neuronal death, neuronal injury, and alteration of neuronal networks, depending on the type and duration of seizures.
Trinka E. 2015

6. Conceptual definition with two operational time points
Onset t1 t2
Length of the seizure and the time
point (t1) beyond which the seizure
should be regarded as
“continuous seizure activity.”
The time of ongoing seizure activity
after which there is a risk of
long-term consequences

7. Epidemiology 50 per 100,000 population Highest in children
Bimodal increase in incidence
Significant mortality
22%-23% for children
26% for adults
Neurological morbidity in 11-16%
Refractory SE (RSE) is common (31-44%)

8. Stages of SE Early phase Stage 1 Premonitory SE, Impending SE
5-10
min
Established SE
10-30
min
Stage 2
Refractory SE
Subtle SE, stuporous SE
Stage 3
30-120
min
Super-refractory SE : SE that continuous in spite of
treatment with anaesthetics for > 24 hrs
>24 h
Stage 4

9. Scope What is CSE in the ED? What are we dealing with? What do we do?
Operational definition and new definition
What are we dealing with?
Underlying aetiology
What do we do?
Optimal management

10. Underlying aetiology
Commonest single group of causes is acute symptomatic aetiology
Same for adults and children
In adults
CVA commonest in developed countries and elderly
CNS infections commonest in developing countries
Murthy J M K

11. Epilepsy and
Behavior
2015

12. Causes of CSE in children
Hypoxic brain injury
CNS Infections
Traumatic brain injury
Metabolic derangements
CNS demyelinataion
Vascultis, Autoimmune encephalitis
Shorvon S 2006

13. Acute symptomatic (31%)
Febrile status (13%)
Remote symptomatic 4 (13%)
Epilepsy (24%)
Unclassified (06%)
n=29

14. Scope What is CSE in the ED? What are we dealing with? What do we do?
Operational definition
What are we dealing with?
Underlying aetiology
What do we do?
Optimal management

15. Therapeutic principles
Address pathophysiology
GABAA Agonists
NMDA antagonists
multiple receptors or ion channels
Rx plan according to stages
Considerations
ease of administration
onset of action (rapid)
duration of action (intermediate to long)
spectrum of activity (broad)
minimal morbidity

16. Therapeutic principles
Commence rapidly and continue sequentially
Use therapeutic doses ALWAYS
Critical care treatment and monitoring
Treatment of underlying cause
Commencement of neuro-protective mechanisms
Constant management of complications

17. Stages of SE Early phase Stage 1 Premonitory SE, Impending SE
5-10
min
Established SE
10-30
min
Stage 2
Refractory SE
Subtle SE, stuporous SE
Stage 3
30-120
min
Super-refractory SE : SE that continuous in spite of
treatment with anaesthetics for > 24 hrs
>24 h
Stage 4

18. Stages of SE BDZ first choice for out-of- hospital Mx
Early phase (MAY BE PRE or IN HOSPITAL)
Premonitory SE, Impending SE
5-10
min
BDZ first choice for out-of- hospital Mx
IV – Lorazipam (Alldredge BK 2001)
IM – Midazolam
Rectal Diazepam in children (Dreifuss FE 1998)
IV Diazepam
Nasal or buccal – MDZ
(Scott RC 1999, McIntyre J 2005)
Clear benefit of prehospital Rx with LRZ or DZP

19. Early phase SE
Trinka E 2015

20. Key highlights Out of hospital administration
Clear benefit shown due to early SE abolition
Buccal MDM favoured over DZP
In hospital when resuscitation facilities available
Use the IV preparations recommended
Lorazepam favoured

22. Stages of SE Second-line drugs when BDZ fail to terminate
5-10
min
Established SE
10-30
min
Stage 2
water solubility and neutral pH
more rapid administration with
less adverse effects
compatibility with all IV fluids
Second-line drugs when BDZ fail to terminate
IV phenytoin/fosphenytoin
IV phenobarbate
IV sodium valproate
IV leveteracetam
No clear evidence to support one over the other for CSE termination

23. Established status
Trinka E 2015

24. Stages of SE NO RCTs Continuous infusion (cIV) of anesthetic agents:
5-10
min
10-30
min
Stage 3
Refractory SE
Subtle SE, stuporous SE
30-120
min
NO RCTs
Continuous infusion (cIV) of anesthetic agents:
Thiopental/ pentabarbital, midazolam
and propofol (Shorvon S 2012)
Successful Rx with propofol in 2/3 of RSE
For 24–48 hours of electrographic control by cEEG monitoring
Dosing titrated to cessation of electrographic seizures
or burst suppression

26. Propofol: IV bolus 2 mg/kg, repeated if necessary, followed by a continuous infusion of 5–10 mg/kg/hour initially, reducing to maintain a burst suppression (usually 1–3 mg/kg/hour)
Thiopental: IV bolus 100–250 mg given over 20 s with further 50 mg boluses every 2–3 min until seizures are controlled, followed by a continuous IV infusion to maintain a burst suppression (usually 3–5 mg/kg/hour)
Midazolam: IV bolus 0.1–0.3 mg/kg at a rate not exceeding 4 mg/min initially, followed by a continuous IV infusion to maintain a burst suppression pattern (0.05–0.4 mg/kg/hour).

27. Stages of SE
No RCTS
Use different conventional AEDs – TPM (via NG), Lacosamide, LEV
Inhalational agents - isoflurane and desflurane
IVIG, High dose steroids
Ketamine (NMDA receptor Antagonist)
Budesonide
Ketogenic diet
Magnesium Sulphate, pyridoxine
Epilepsy surgery, Vagal nerve stimulation, DBS
5-10
min
10-30
min
30-120
min
Super-refractory SE : SE that continuous in spite of
treatment with anaesthetics for > 24 hrs
>24 h
Stage 4
10-15% of all CSE
Outcome – 35% mortality, 35% recovery to baseline
(Shorvon S 2012)

28. Anaesthetics in SRE How long to use? Complications of anaesthesia
Exotoxic damage already occurred
?Risk of anaesthesia exceed risk of SE?
Complications of anaesthesia
How to cycle?
Initially hour cycles and then longer
Should one switch anaesthetics?
Prolonged propofol carries specific risk
What stage to switch ??
NO DATA ON THESE POINTS

29. Anti Epileptic drug therapy
Approach to use AEDs in SRE (via NG / PEG)
Purpose – coverage when anaesthetic effects are withdrawn
Principles
Polytherapy with two
High dose
Avoid frequent switching
Favour those with lower interaction potential, predictable kinetics and without renal or hepatic toxicity
Avoid GABAergic AEDs

30. Concommittent multimodal approach

31. Common reasons for treatment failure
Under-dosing at the stage of established SE
Neglecting maintenance therapy
Misdiagnosis- i.e. psychogenic nonepileptic status, drug-induced or metabolic encephalopathy
Failure to identify and treat the underlying etiology
Failure to address Iry complications

32. Continuous EEG (cEEG) monitoring
Initiated for RSE (after one hour)
Useful for titration of other maintenance AEDs
Duration – at least 48 hours if NCSE
treatment endpoints for cEEG monitoring
cessation of nonconvulsive seizures
diffuse beta activity
burst suppression 8–20 seconds’ intervals
complete suppression of EEG

33. Supportive management
Assisted ventilation and cardiovascular monitoring
Vasopressor agents
Cerebral oedema lowering agents
Continuation of maintenance AEDs
Brain cooling

34. Systemic complications of SRE
Complications due to therapy with inhalational Anaesthetics
Hypothermia, infection, death
Complications due to prolonged ICU stay and immobility
PE, DVT
Pulmonary complications
Sepsis,colitis
Skin complications, fungal infections
Critical illness nopathy/ neuropathy

35. Systemic complications of SRE
Complications due to status and treatment
Complications due to treatment

36. Prognostic factors Poor outcome related to underlying etiology
de novo development of SE in hospitalized patients
older age
impairment of consciousness
duration of seizures
focal neurological signs at onset
presence of medical complications

38. Summary What is CSE in the ED? What are we dealing with?
Operational definition
What are we dealing with?
Underlying aetiology
What do we do?
Optimal management