2. Seizure
paroxysmal disorder of CNS (grey matter) –abnormal
neuronal discharge- change in function of pt.
Excessive hypersynchronous discharge of cortical
neurons in grey matter.
Risk factors- fever, hyponatremia, hypoglycemia,
hypocalcemia, meningitis, head trauma, toxins,
ethanol.
DDs- syncope, breath holding spells, movement
disorders, hyperventilation syndrome.
3. Status epilepticus
Old defn.
seizure lasting > 30 min
recurrent seizures lasting >30 min, without pt. regaining
consciousness.
Current defn.
seizure >= 5 min of continuous seizures.
or
2 or more discrete seizures - incomplete recovery of
consciousness .
4. Classification of SE
Gen. Convulsive- overt
(CSE) - subtle
Non convulsive SE
(NCSE ) - assoc. coma or paralysis
- following prolonged convulsion
- Absence SE
Focal - simple
- complex
5. Classification of SE- cause
Symptomatic SE- known cause for SE (structural or
metabolic ).
Acute symptomatic SE - < 7 days to acute systemic
metabolic or toxic insult or acute CNS insult.
Remote symptomatic SE - > 1 week , remote CNS injury-
infection, trauma, cerebrovascular d/s, cortical dysgenesis.
Idiopathic SE- no known or suspected cause for seizures.
6. Proportional incidences for symptomatic
epilepsies
Cerebral malformations- 40-45 %
Infections- 25 %
Head trauma- 15 %
Strokes- 5-7 %
Others- 10-12 %
( Major P, Thiele EA. Seizures in children determining
the variation. Pediatr Rev. 2007; 28: 363-371 )
7. Physiological derangements in status
epilepticus
Blood pressure: Hypertension, Hypotension
PaO2: Hypoxia
PCO2: Increased ICP
Serum pH: Acidosis
Automatic: Arrhythmias
Potassium: Arrhythmias
Creatine kinase: Renal failure
Cerebral blood flow: Central nervous system bleed
Cerebral metabolic rate of O2 consumption: Ischemia
( Textbook of Pediatric intensive care
medicine.Baltimore: Williams & Wilkins; 1987:618. )
8. Causes
Causes of SE in Children ( Richmond, Virginia,
1996 study )
Infection with fever.
Remote symptomatic cause.
Low anti convulsant drug levels.
Causes of SE in adults
Low anti convulsant levels.
Remote symptomatic cause.
Stroke.
12. Epilepsy
Chronic seizure disorder- recurrent (more than two )
unprovoked seizures –predisposition-underlying state.
Long term complication of SE, refractory SE, SRSE.
13.
14. Super refractory SE
SE continues 24 hours or more after onset of
anesthetic therapy OR
SE recurs during reduction or withdrawal of
anesthesia.
15. Non convulsive status epilepticus (NCSE)
Clinically subtle or non convulsive seizures –common
in ICU pts. –following prolonged convulsive seizures.
Needs cEEG monitoring.
17. Normal neuronal firing
Neuron with one Excitatory (E) & one Inhibitory (I)
input.
Right side of graph –Membrane potential (mV) –
beginning at Resting membrane potential (-70 MV)
Activation of E- graded Excitatory post synaptic
potential ( epsp )- larger one reaches threshold (-40
MV)- Action potential.
18. Action potential- followed by After
hyperpolarization (AHP).
Magnitude of AHP – determines next action potential.
Activation of I- Inhibitory post synaptic potential
( ipsp ).
19. Neuronal membrane
Magnified portion of neuronal membrane- lipid
bilayer- interposed voltage gated Na & K channels.
Direction of ion fluxes Na to inside & K to outside.
Membrane bound Na K pump & astroglial cells-
restore ionic balance, after firing.
21. Abnormal neuronal firing
Abnormal neuronal firing- at levels of Brain &
Neuronal network.
Two Excitatory neurons (1 & 2) and one Inhibitory
neuron (3).
EEG & intracellular recordings –shown for normal,
interictal & ictal conditions.
22. Abnormal neuronal firing
Brain
Three EEG electrode record activity –from superficial
neocortical neurons.
Normal case- low voltage activity & desynchronized-
neurons are not firing .
Interictal cond.- large spikes focally at electrode 2-
electrode 1 , lesser extent- sharp waves.
Ictal state- long run of spikes.
23. Abnormal neuronal firing
Neuronal network
Paroxysmal depolarization shift (PDS)-
intercellular correlate of interictal EEG spike.
PDS – initiated by Non NMDA mediated fast epsp &
maintained by longer NMDA mediated epsp.
Post PDS hyperpolarization- stabilizes neuron.
Post PDS hyperpolarization fails- ictal discharge
occurs.
24. Lower most traces- recordings from neuron 2- activity
similar to neuron 1.
25. Neurophysiology
Seizures- abnormal synchronous electrical discharge
(depolarization)- of a group of neurons in CNS.
Depolarization- influx of Na into neuron .
Repolarization- egrees of K from cell- restoration of
resting negative electrical potential.
Electrical potential- regulated by sodium potassium
pump- ATP driven.
26. GABA- major inhibitory neurotransmitter in CNS.
GABA receptors have chloride ion channel complex &
binding sites for barbiturates & benzodiazepines.
Glutamate- excitatory neurotransmitter of CNS-
effects on NMDA & non NMDA receptors & secondary
messenger systems.
41. BURST SUPPRESSION EEG
EEG pattern- high voltage electrical activity-
alternating with periods of no activity in brain.
Brief bursts- mixture of spikes, sharp waves,
alternating with very low voltage.
Inactivated brain states- general anesthesia, coma,
hypothermia.
Marker for level of coma , a pt. is in.
44. ISOELECTRIC EEG PATTERN
Complete loss of cortical electrical activity –with
maximal amplification .
If sustained for 1 hour or more- cerebral death
47. Non epileptiform abnormalities- not necessarily
assoc. with seizure- suggest CNS dysfunction.
Slow waves – nonspecific ( may show structural or
functional abnormality )- seen after a seizure or SE.
Location of slow waves- differentiation b/w
generalized & focal seizures.
Generalized slow waves- assoc. diffuse encephalopathy
– metabolic disturbance, hypoxia-ischemia, post ictal
state.
48. Sustained Refractory SE
SE > 24 hrs.
Prolonged therapy may be needed for days to weeks
High dose seizure suppression medications.
49. Rx of SE - goal
Abort seizure before irreversible neuronal injury
occurs .
SE may be difficult to control once its duration
increases .
50. General supportive measures
Airway
Breathing
Circulation
In case of intubation ( use only short acting relaxant
and sedative ).
Check vitals – HR , RR , BP, Temp, O2 saturation.
GRBS –finger stick blood glucose- Rx if needed.
54. URGENT CONTROL THERAPY
Phenytoin 20mg/kg iv (another 10mg/kg if needed) –
may cause arrhythmia, hypotension, purple glove
syndrome.
OR Fosphenytoin 20 PE/kg iv (another 10 PE/kg if
needed).
OR consider Phenobarbital, Valproate sodium, or
Levetiracetam.
If <2 yrs , consider Pyridoxine 100 mg iv.
55. REFRACTORY STATUS EPILEPTICUS
If seizures continue after Benzodiazepines & second
antiseizure medication.
Continuous EEG monitoring.
Leviteracetam 20-60 mg/kg iv.
Valproate sodium 20-40 mg/kg iv – ( contraindicated
if liver disease, thrombocytopenia, metabolic d/s).
Phenobarbital 20-40 mg/kg iv- (cause respiratory
depression, hypotension).
57. REFRACTORY SE
PHARMACOLOGICAL COMA MANAGEMENT
Titrate to seizure suppression or burst suppression
based on EEG.
Continue pharm. coma for 24-48 hrs.
Modify antiseizure medications – for infusion
wean.
Continue diagnostic testing & etiology directed
therapy.
62. BENZODIAZEPINES
Lorazepam, Diazepam, Midazolam.
1st line agents- RX of SE.
Enhances inhibitory neurotransmission.
Binds to specific BZD site on GABAa receptor.
DOC – Lorazepam ??
Less respiratory depression
Prolonged antiepileptic effect- more than 6 hrs.
Diazepam- less than 1 hr.
Less lipophilic ( as diaz is highly protein bound )
Preferred route – IV
Diazepam –IM, PR
Midazolam –IM, intranasal spray, buccal.
63. Barbiturates
Increase inhibitory neurotransmission at GABAa.
Phenobarbital, Pentobarbital, Thiopental.
Phenobarbital– 2nd line drug after bzd do not abort
seizure.
Good efficacy against – GTCS, AS, myoclonic & focal
seizures.
Drawbacks – sedation , resp. depression , hypotension.
64. Phenytoin
Inhibits voltage gated sodium channels
Blocks fast repititive firing of neurons
Adv – minimal sedation & resp depression
Adverse effects– dysarthria, ataxia, hypotension,
cardiac arrhythmias , infusion site pain ,
thrombophlebitis and extravasation causing Purple
glove syndrome .
Max infusion rate is 1 mg/kg/min (max 50 mg/min )
65.
66. Fosphenytoin
Water soluble disodium phosphate ester of phenytoin.
IM / IV
Devoid of propylene glycol- administered at faster
rate- no cardiovascular risks & no extravasation.
15-20 mg PE/kg iv – initial dose.
Max infusion rate of 150 mg PE/min.
No side effects of phenytoin.
67. Paraldehyde
Alternative to phenytoin and pheno in early SE or RSE.
Wide spectrum & efficacy
200-400 mg/kg PR.
Irritant effect on rectal mucosa ( disadv)
No IV
Pulmonary toxicity
68. REFRACTORY SE
Continued SE despite administration of multiple first
& second line agents – benzodiazepines,
fosphenytoin, phenytoin, phenobarbitone.
SE persists beyond 1 yr despite AED therapy.
Continuous seizure activity ( clinical or
electrographical) for hours.
24 hr cEEG monitoring.
69.
70. Rx of RSE
Role of conventional AED’s ( Topiramate, CBZ,
Levetiracetam ).
Therapeutic options in RSE – high dose BZD ,
barbiturates , propofol , valproic acid , ketamine ,
lidocaine & inhalational anaesthetic agents.
71. Goals of RSE
Termination of all clinical & electrographic seizure
activity .
Achieve burst suppression pattern on EEG – maintain
for at least 12 hrs before tapering medication.
If seizure recurs while tapering – maintain therapy for
48hrs before tapering.
Also titrate conventional AED’s to high therapeutic
doses.
72. High dose barbiturates
Pentobarbital, Thiopental, Phenobarbital.
Pentobarbital – loading dose- 5-10 mg/kg IV &
continuous infusion 1 mg/kg/hr ( max 10 mg/kg/hr).
Rx of break through seizure - 3-5 mg/kg bolus.
High dose Phenobarbital – incremental boluses of 10
mg/kg.
(no max level or dose . give until seizures are
suppressed). serum levels- 344 mg/ml ( 1490 mmol/l).
Drawbacks : cardiovascular depression & hypotension
and immunosuppression.
73. High dose BZD
Midazolam – 0.15 mg/kg LD & continuous infusion @
1 mcg/kg/min ( max of 24 mcg/kg/min)
Rapid onset , short half life , less CVS depression
Adverse effects : tachyphylaxis.
74.
75. Propofol
GABAa agonist.
Rapid onset of action , short half life.
Bolus dose of 1-2 mg/kg & continuous infusion of 1-2
mg/kg/hr.
Adverse effects – resp. depression & hypotension-
myocardial depression.
Propofol infusion syndrome ( metabolic acidosis,
lipemia ,rhabdomyolysis , bradyarrhythmias & death ).
76.
77. Valproic acid
Role in RSE.
Generalized convulsive & nonconvulsive seizures.
Loading dose- 20 mg/kg & infusion @ 1-4 mg/kg/hr
depending on pts hepatic induction.
78. Inhalational anaesthetics
Halothane, Isoflurane.
Halothane- advantage of easily titrable.
Risk of organotoxicity on prolonged use.
Hemodynamic compromise.
Isoflurane- achieves isoelectric EEG at 1.5 %- 2 %.
79. Ketamine and lidocaine
Ketamine – NMDA antagonist having both
anticonvulsant & neuroprotective properties
Good therapeutic option - refractory SE - failed to
high dose BZD & barbiturates.
Lidocaine- IV bolus & continuous infusion.
80. Pyridoxine
Vitamin B6
Cofactor for glutamic acid & decarboxylase & GABA
transaminase.
Trial of pyridoxine - child < 3 yrs with recurrent
seizures or SE - if seizures refractory to conventional
anticonvulsants .
Isoniazid poisoning –effective anticonvulsant.