1. Kaj Sep Nellie Mags
STATUS EPILEPTICUS

2. SEIZURE
Paroxysmal, abnormal, excessive, excessive neuronal discharge arising from the brain
Capable of causing alteration in function and/or behavior

3. STATUS EPILEPTICUS
“seizure that persists for a sufficient length of time or is repeated frequently enough to produce an enduring epileptic condition”
Recurrent seizures without complete recovery of consciousness between attacks or virtually continuous seizure activity for more than 30 min with or without impairment of consciousness

4. Any seizure lasting more than 5 minutes or two or more discrete seizures between which there is incomplete recovery of consciousness
Seizures lasting longer than 10 minutes or seizures on presentation at the ER or recurring in the ER

5. REFRACTORY SE
Seizure that continues and fails to respond to appropriate first line drug therapy and persists for longer than 60 minutes

6. ETIOLOGY Genetic and birth factors (eg Anoxia) CNS Infection
Head trauma
Circulatory disturbances (syncope)
Neoplasms
Metabolic or nutritional deficiencies (Hypoxia, Hypoglycemia
Eclampsia
Toxic factors (Abrupt withdrawal of alcohol or drugs)
Unknown causes

7. PATHOGENESIS
Cellular ischemic changes begin to occur in 15 to 30 minutes of seizure and irreversible damage begins to occur in 90 to 120 minutes of continuous seizures
Damage in SE is due to combined effects of:
Hypoxia
Hypotension
Hyperthermia
Hypoglycemia
Acidosis

8. TREATMENT GOALS Immediate termination of seizure ABCs of life
Identification and treatment of cause

9. SUGGESTED PROTOCOL FOR SE
TIME
ACTION
0 to 5 minutes
Diagnose by clinically observing patient
Maintain good airway. Give oxygen by nasal cannula or mask; position patient’s head for optimal airway patency; consider intubation
VS, control any abnormalities, ECG monitoring
IV line; draw blood for glucose level, serum chemistries, hematology studies, toxicology screen and determination of AED level

10. Assess oxygenation with oximetry or ABG
TIME
ACTION
6 to 9 minutes
Assess oxygenation with oximetry or ABG
If hypoglycemia is established give glucose solution
Diazepam 5mg/IV – can be repeated if seizures do not stop after 5 minutes
DIAZEPAM – advantage of stopping seizures in 3 minutes in a third of cases; greatest drawvack – short lived effect

11. TIME
ACTION
10 To 20 minutes
If diazepam is used to stop SE, phenytoin should be administered to prevent recurrence
If seizures persist, infuse mg/kg phenytoin very slow IV push, monitor HR
Fosphenytoin is the ideal drug – long duration of action, does not impair consciousness

12. TIME
ACTION
21 to 60 minutes
- If seizures persist, give another 10mg/kg of phenytoin
>60 minutes
If seizures do not stop after 30mg/kg of phenytoin – phenobarbital 20 mg/kg IV or barbiturate drip (pentobarbital coma)

13. Treatment  Excitatory neurotransmission
 Inhibitory neurotransmission

14. Pharmacologic Therapy
First line treatment: drugs that stop SE as fast as possible within a few minutes (diazepam, lorazepam)
Second line treatment: drugs that prevent recurrence of seizures and stop SE if the first line fails (phenytoin, phenobarbital, valproic acid)

16. Anti-epileptic Drugs Type I – blockade of Na channel
Type 2 – enhancing post-synaptic GABA receptor current
Type 3 – inhibition of low threshold Ca++ current
Type 4 – inhibition of excitatory amino acids or neurotransmission by NMDA and non-NMDA receptor antagonism

17. Phenytoin : type I Antiarrhythmic Trigeminal neuralgia Migraine
Status epilepticus

18. Phenytoin
Slows the rate of recovery of voltage-activated sodium channels
Blocks sustained high-frequency repetitive firing of action potentials

19. Phenytoin At high concentrations:
Inhibits release of serotonin, norepinephrine
Inhibits calcium influx
Promotes uptake of dopamine

20. Phenytoin: Cardiovascular complications
Nystagmus
Diplopia & ataxia
Mental changes, lethargy & dysarthria
Stupor
Gingival hyperplasia
Hirsutism
Skin rashes (purple glove syndrome)
Fetal Hydantoin syndrome: craniofacial abn, nail & digit hypoplasia, MR, microcephaly
Chronic use:
Osteomalacia
Megaloblastic anemia

21. Phenytoin
loading dose: mg/kg administered at a maximal rate of 50 mg/min
an additional 10 mg/kg may be given because many patients may require serum levels of approximately 25 to 30 µg/mL to achieve seizure control
BP and ECG monitoring

22. Fosphenytoin: administered at a maximal rate of 150 mg of phenytoin equivalent/min
More expensive
Better pharmacokinetic profile

23. Phenobarbital: type 2 AED
Generalized tonic-clonic seizures
Febrile seizure prophylaxis
Status epilepticus

24. Phenobarbital increasing GABA-A mediated cellular inhibition
Its mechanism of action is similar to benzodiazepines but involves a different isoform of the GABAA receptor

25. Phenobarbital At high concentration: Serious adverse effects:
Suppresses high frequency repetitive firing – Na blockade
Block Ca currents
Blocks excitatory response induced by glutamate
Serious adverse effects:
half-life of more than 48 hours

26. Phenobarbital Repiratory depression CNS depression
Severe hypotension secondary to peripheral vasodilation and decreased cardiac contractility
Nystagmus
Ataxia
Rash
Megaloblastic anemia

27. SE loading dose: 15-20 mg/kg by IV push Maintenance: 0.5-5mg/kg/h
Monitor BP, ECG, respiratory function

28. Benzodiazepines GABA-A receptor agonist
For status epilepticus and act as adjunctive therapy with other convulsants
Sedation, development of tolerance

29. Benzodiazepines
GABA-induced opening of chloride channels allowing intracellular chloride influx causing hyperpolarization
 Inhibitory neurotransmission

30. Benzodiazepines Fast onset of action
Highly lipid soluble, redistributed rapidly to peripheral fat stores
clinical effectiveness: minutes
Diazepam, lorazepam, midazolam

31. Benzodiazepines CNS Depression Respiratory depression Hypotension
Teratogenic – oral clefts, 1st trimester use

32. Diazepam: IV push 0.2mg/kg at 5mg/min with maximum dose of 20mg
Lorazepam: IV push 0.1mg/kg at 2mg/min with maximum dose of 8mg
Midazolam: 0.2mg/kg bolus injection followed by infusion of mg/kg/h)

33. Refractory SE
seizures recalcitrant to standard loading doses of anticonvulsant medications require treatment with anesthetic doses of benzodiazpines, short-acting barbiturates, or propofol

34. Midazolam: loading dose of 0
Midazolam: loading dose of 0.2 mg/kg and is maintained at a continuous infusion of 0.05 to 2.0 mg/kg/h
Rapid and effective
Favorable pharmacologic profile

35. Propofol: loading dose of 3 to 5 mg/kg is given slowly followed by an infusion of 1 to 15 mg/kg/h
short-acting nonbarbiturate hypnotic used to induce general anesthesia
GABA A agonist
Rapid induction and elimination
Propofol infusion syndrome: hypotension, lipidemia and metabolic acidosis

36. Barbiturates
Pentobarbital: loading dose of 5 to 15 mg/kg over 1 hour and is maintained at an infusion dosage of 0.5 to 10.0 mg/kg/h
Thiopental is given as needed in 75- to 125-mg IV boluses maintained between 1 and 5 mg/kg/h

38. THANK YOU!