Seizure/Status Epilepticus

Question 1

Provoked seizures

Answer 1

intoxication
withdrawal (benzo, alcohol)
trauma
meningitis
psychiatric
metabolic derangements

Question 2

Unprovoked seizures

Answer 2

may or may not need treatment
first time unprovoked does not require medication

Question 3

Seizure physiology

Answer 3

mismatch of normal inhibitory mechanisms which are responsible for preventing/terminating seizures
GABA (inhibitory)
Glutamate, aspartate, ach (exitatory_

Question 4

Seizure Epidemiology

Answer 4

most are self limited
30 day mortality of generalized convulsive status epilepticus is 20%
rapid control of seizures fundamental to tx

Question 5

Status epilepticus definition

Answer 5

old: >30 min
new: > 5 min

Question 6

Seizure pharm goals

Answer 6

rapid/safe termination of seizure
prevent reoccurence
Avoid CV or respiratory ADRs

Question 7

Drugs to stop seizure

Answer 7

Benzodiazepines (MLD)
Lorazepam
Diazepam
Midazolam

Question 8

Drugs to prevent seizure

Answer 8

Phenytoin
Fosphenytoin
levetiracetam
valproic acid

Question 9

Stage 1 seizure

Answer 9

airway, circulation, lab test, IV thiamine, then dextrose

IV lorazepam or midazolam repeat if needed

0 to 10 min

Question 10

Stage 2 seizure

Answer 10

Phenytoin or fosphenytoin

Alt:
VPA, phenobarbital, levetiracetam

10 to 30 min

Question 11

Stage 3 seizure

Answer 11

Midazolam or Propofol
IV infusion
* if intubated = paralyzed, get LTM via EEG

30 min to 90 min

Question 12

Stage 4 seizure

Answer 12

Pentobarbital

90 min to hours/days

Question 13

Benzodiazepines first line choice

Answer 13

IV lorazepam 0.1-0.2 mg/kg
(4mg)

Question 14

Benzodiazepines second line choices

Answer 14

Diazepam IV
0.15mg/kg (5-20mg)
Midazolam IM
0.15-0.20 mg/kg (10mg)

diazepam PR for outpatient

Question 15

Benzodiazepines ADR

Answer 15

impaired consciousness (20-60%)
Respiratory depression (3-10%)
hypotension (<2%)

Question 16

Benzodiazepines MOA

Answer 16

bind GABA = increase gaba-ergic transmission

Question 17

Fos(Phenytoin) MOA

Answer 17

stabilizes neuronal membrane
increase efflux Na
Decrease influx Na

Question 18

Fos(Phenytoin) Dosing

Answer 18

LD: 20mg/kg (max 50mg/min)
MD: 4-6 mg/kg/day divided 2-3 doses

Question 19

Fos(Phenytoin) PK

Answer 19

highly protein bound (90%)
uremia increases [free]
Peak [brain] = 6 min after infusion completed
Liver: hydroxylation (primary)
MM kinetics: saturable PK

Question 20

Fos(Phenytoin) ADR

Answer 20

CV: Na blocker (arrythmia, hypotension, bradycardia, QTc prolongation)
Extravasation (poor IV access)
Rashes/fever/SJS
Neutropenia/ thrombocytopenia

PHENYTOIN mneumonic

Question 21

PHENYTOIN ADR Mneumonic

Answer 21

P-450
Hirsutism/hypertrichosis
Enlarged gums
Nystagmus
Yellow-browning skin (hepatitis)
Teratogenicity
Osteomalacia (D deficiency)
Interfere folate metabolism (anemia)
Neuropathies (ataxia, headache, vertigo)

Question 22

Phenytoin CV ADR cause

Answer 22

Incidence correlated to infusion rate
Attributable to diluent: propylene glycol

Question 23

Fos(Phenytoin) monitoring

Answer 23

Goal 10-20 mcg/dL total
if seizing: higher goal 15-25
level >30 = seizures
Correct for low albumin (<3.5) & CrCL<30

Question 24

Levetiracetam MOA

Answer 24

binds to SV2A (synaptic vessel protein)
involvement in NT release

NT = neurotransmitter

Question 25

Levetiracetam Dosing

Answer 25

Status epilepticus: 60 mg/kg IV bolus (max 1000mg IV BID) | CKD AKU adjust, except active SE

Question 26

Levetiracetam monitoring

Answer 26

Don't get level - doesnt correlate with efficacy only get level to verify compliance

Question 27

Levetiracetam ADR

Answer 27

Agitation Drowsiness

Question 28

VPA MOA

Answer 28

MORE GABA Less exitatory AA Less NMDA excitation Blocks voltage dependent NA channels = inhibit excitable membranes

Question 29

VPA dosing

Answer 29

LD: 40mg/kg (max 3000 mg) MD: 5mg/kg IV Q8H | increase MD based on levels

Question 30

VPA PK and DDI

Answer 30

Highly protein bound VPA will displace phenytoin = more free phenytoin = toxicity

Question 31

VPA ADR

Answer 31

drowsiness, headache thrombocytopenia pancreatitis (peds) hyperammonemia

Question 32

Lacosamide MOA

Answer 32

stabilize neuronal membrane inhibit repetitive neuronal firing Enhances slow inactivation of Na channels

Question 33

Lacosamide dosing

Answer 33

100 - 200 mg IV BID

Question 34

Lacosamide ADR

Answer 34

well tolerated dizziness, abnormal vision, diplopia, ataxia | bradycardic arrythmias, avoid if hx

Question 35

Refractory status epilepticus definition

Answer 35

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

Question 36

Refractory status epilepticus Tx

Answer 36

1. High dose BZD * Midazolam bolus + cont infusion * 2mg IV bolus + 2mg/kg/hr, double infusion prn up to 64 mg/kg/hr 2. Propofol IV infusion - watch LTM 3. Last line: phenobarbital/pentobarbital coma

Question 36

Post intubation SE tx

Answer 36

1. start IV antiepileptic (propofol/midazolam) 2. 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

Question 37

Phenobarbital/Pentobarbital Coma MOA

Answer 37

sensory cortex supression (sedative hypnotic) shuts brain down

Question 38

Phenobarbital dosing

Answer 38

LD: 20mg/kg IV x 1 MD: 1-2 mg/kg IV twice daily

Question 39

Pentobarbital dosing

Answer 39

5-15 mg/kg IV x 1 0.5-5mg/kg/hr IV infusion

Question 40

Phenobarbital/Pentobarbital Coma ADR

Answer 40

IV - respiratory depression Hypotension - pressors lethargy nystagmus thrombocytopenia decreased GI motility supress immune system (watch for infection labs, pt won't spike fever)

Question 41

SE Tx goal

Answer 41

attain burst supression on LTM for 24-48 hours slowly titrate off IV infusion while monitoring LTM for reoccurrence

Question 42

SUPER refractory SE Tx | pt in barb induced coma and still seizing

Answer 42

Ketamine infusion (NMDA antagonist) LD: 1.5 - 3 mg/kg IV x 1 MD: 0.1-4mg/kg/hr (max 15 mg/kg/hr)

Question 43

How to wean drugs after attaing burst supression

Answer 43

Wean ADR causing drugs first - barbituates, propofol (results in need for pressors) - Midazolam (accumulates in fat)

Question 44

SE outcomes

Answer 44

Post ictal - repeat neuro exam, investigate cause of seizure

Question 45

Mortality of SE

Answer 45

non-convulsive: 51% refractory: 19-60%