Seizure/Status Epilepticus Flashcards
Provoked seizures
intoxication
withdrawal (benzo, alcohol)
trauma
meningitis
psychiatric
metabolic derangements
Unprovoked seizures
may or may not need treatment
first time unprovoked does not require medication
Seizure physiology
mismatch of normal inhibitory mechanisms which are responsible for preventing/terminating seizures
GABA (inhibitory)
Glutamate, aspartate, ach (exitatory_
Seizure Epidemiology
most are self limited
30 day mortality of generalized convulsive status epilepticus is 20%
rapid control of seizures fundamental to tx
Status epilepticus definition
old: >30 min
new: > 5 min
Seizure pharm goals
rapid/safe termination of seizure
prevent reoccurence
Avoid CV or respiratory ADRs
Drugs to stop seizure
Benzodiazepines (MLD)
Lorazepam
Diazepam
Midazolam
Drugs to prevent seizure
Phenytoin
Fosphenytoin
levetiracetam
valproic acid
Stage 1 seizure
airway, circulation, lab test, IV thiamine, then dextrose
IV lorazepam or midazolam repeat if needed
0 to 10 min
Stage 2 seizure
Phenytoin or fosphenytoin
Alt:
VPA, phenobarbital, levetiracetam
10 to 30 min
Stage 3 seizure
Midazolam or Propofol
IV infusion
* if intubated = paralyzed, get LTM via EEG
30 min to 90 min
Stage 4 seizure
Pentobarbital
90 min to hours/days
Benzodiazepines first line choice
IV lorazepam 0.1-0.2 mg/kg
(4mg)
Benzodiazepines second line choices
Diazepam IV
0.15mg/kg (5-20mg)
Midazolam IM
0.15-0.20 mg/kg (10mg)
diazepam PR for outpatient
Benzodiazepines ADR
impaired consciousness (20-60%)
Respiratory depression (3-10%)
hypotension (<2%)
Benzodiazepines MOA
bind GABA = increase gaba-ergic transmission
Fos(Phenytoin) MOA
stabilizes neuronal membrane
increase efflux Na
Decrease influx Na
Fos(Phenytoin) Dosing
LD: 20mg/kg (max 50mg/min)
MD: 4-6 mg/kg/day divided 2-3 doses
Fos(Phenytoin) PK
highly protein bound (90%)
uremia increases [free]
Peak [brain] = 6 min after infusion completed
Liver: hydroxylation (primary)
MM kinetics: saturable PK
Fos(Phenytoin) ADR
CV: Na blocker (arrythmia, hypotension, bradycardia, QTc prolongation)
Extravasation (poor IV access)
Rashes/fever/SJS
Neutropenia/ thrombocytopenia
PHENYTOIN mneumonic
PHENYTOIN ADR Mneumonic
P-450
Hirsutism/hypertrichosis
Enlarged gums
Nystagmus
Yellow-browning skin (hepatitis)
Teratogenicity
Osteomalacia (D deficiency)
Interfere folate metabolism (anemia)
Neuropathies (ataxia, headache, vertigo)
Phenytoin CV ADR cause
Incidence correlated to infusion rate
Attributable to diluent: propylene glycol
Fos(Phenytoin) monitoring
Goal 10-20 mcg/dL total
if seizing: higher goal 15-25
level >30 = seizures
Correct for low albumin (<3.5) & CrCL<30
Levetiracetam MOA
binds to SV2A (synaptic vessel protein)
involvement in NT release
NT = neurotransmitter
Levetiracetam Dosing
Status epilepticus: 60 mg/kg IV bolus (max 1000mg IV BID)
CKD AKU adjust, except active SE
Levetiracetam monitoring
Don’t get level - doesnt correlate with efficacy
only get level to verify compliance
Levetiracetam ADR
Agitation
Drowsiness
VPA MOA
MORE GABA
Less exitatory AA
Less NMDA excitation
Blocks voltage dependent NA channels = inhibit excitable membranes
VPA dosing
LD: 40mg/kg (max 3000 mg)
MD: 5mg/kg IV Q8H
increase MD based on levels
VPA PK and DDI
Highly protein bound
VPA will displace phenytoin = more free phenytoin = toxicity
VPA ADR
drowsiness, headache
thrombocytopenia
pancreatitis (peds)
hyperammonemia
Lacosamide MOA
stabilize neuronal membrane
inhibit repetitive neuronal firing
Enhances slow inactivation of Na channels
Lacosamide dosing
100 - 200 mg IV BID
Lacosamide ADR
well tolerated
dizziness, abnormal vision, diplopia, ataxia
bradycardic arrythmias, avoid if hx
Refractory status epilepticus definition
no repsonse to initial anticonvulsants
1. seizure >2 hrs
OR
2. rate of 2+ seizure/hr w/o recovery to baseline despite AED tx
respiratory/cv compromise + systemic complications
Refractory status epilepticus Tx
- High dose BZD
* Midazolam bolus + cont infusion
* 2mg IV bolus + 2mg/kg/hr, double infusion prn up to 64 mg/kg/hr - Propofol IV infusion - watch LTM
- Last line: phenobarbital/pentobarbital coma
Post intubation SE tx
- start IV antiepileptic (propofol/midazolam)
- long term EEG monitoring
Unable to tell if seizing due to paralytic use for intubation
pt usually on 2-3 IV AED + 1≥ cont IV infusion
Phenobarbital/Pentobarbital Coma MOA
sensory cortex supression (sedative hypnotic)
shuts brain down
Phenobarbital dosing
LD: 20mg/kg IV x 1
MD: 1-2 mg/kg IV twice daily
Pentobarbital dosing
5-15 mg/kg IV x 1
0.5-5mg/kg/hr IV infusion
Phenobarbital/Pentobarbital Coma ADR
IV - respiratory depression
Hypotension - pressors
lethargy
nystagmus
thrombocytopenia
decreased GI motility
supress immune system (watch for infection labs, pt won’t spike fever)
SE Tx goal
attain burst supression on LTM for 24-48 hours
slowly titrate off IV infusion while monitoring LTM for reoccurrence
SUPER refractory SE Tx
pt in barb induced coma and still seizing
Ketamine infusion (NMDA antagonist)
LD: 1.5 - 3 mg/kg IV x 1
MD: 0.1-4mg/kg/hr (max 15 mg/kg/hr)
How to wean drugs after attaing burst supression
Wean ADR causing drugs first
- barbituates, propofol (results in need for pressors)
- Midazolam (accumulates in fat)
SE outcomes
Post ictal - repeat neuro exam, investigate cause of seizure
Mortality of SE
non-convulsive: 51%
refractory: 19-60%
