Seizures & Status Epilepticus

Question 1

What are triggers that may provoke a seizure? (7)

Answer 1

• drug/EtOH intoxication
• drug/EtOH withdrawal
• Trauma
• Meningitis
• Psychiatric
• Metabolic derangements
• Non-compliance w/ antiepileptics

Question 2

What are inhibitory (1) and excitatory (3) neurotransmitters that

Answer 2

Inhibitory: GABA
Excitatory: glutamate, aspartate, acetylcholine

Question 3

What is the current definition of status epilepticus?

Answer 3

A seizure lasting >5 minutes

Question 4

What are first line agents for status epilepticus (acutely and long-term)?

Answer 4

ACUTE: BZDs (lorazepam*, diazepam, midazolam)
- stop active seizure!

CHRONIC: antieileptics (phenytoin, fosphenytoin, Keppra, valproic acid)
- prevention of future seizures only!

*= most preferred by guidelines

Question 5

What is the MOA of phenytoin/fosphenytoin?

Answer 5

MOA: stabilize neuronal membrane by MORE efflux or LESS influx of Na+ (less activity)

Question 6

Phenytoin has a lot of AEs. What are they? (8)

Answer 6

P-450 DDIs
Hirsutism
Enlarged gums (gingival hyperplasia)
Nystagmus
Yellowing of skin (hepatitis)
Teratogenic
Osteomalacia (Vit D deficiency)
Interference w folate metabolism (anemia)
Neuropathies (vertigo, ataxia, HA)

Rashes/fever, SJS
Arrhythmias (QT prolongation, bradycardia)
Neutropenia
Thrombocytopenia

Question 7

How is phenytoin primarily metabolized?

Answer 7

Hepatic

Question 8

With significant accumulation, what is the goal trough level of phenytoin? At what level does the drug actually CAUSE seizures?

Answer 8

GOAL: 10-20 mcg/dL trough

Levels >30 = increased seizure risk

Question 9

T/F: Phenytoin is highly lipid-bound, causing more accumulation in obese patients

Answer 9

FALSE: it is actually highly PROTEIN bound (90%!)

Question 10

Levetiracetam, valproic acid, and lacosamide have similar clinical efficacy at preventing seizures as phenytoin. What are the mechanisms of each? Which has a DDI with phenytoin?

Answer 10

Keppra MOA = unknown
VPA MOA = increased GABA synthesis/release, reduced excitatory AAs
Lacosamide MOA = stabilizes hyperexcitable neuronal membranes & inhibits repetitive neuronal firing
VPA has DDI w phenytoin

Question 11

What defines refractory status epilepticus?

Answer 11

Seizure lasting >2 hrs
OR
2+ recurrent seizures per hour without recovery to baseline despite antiepileptic use

Question 12

If a patient is intubated & paralyzed during a seizure, how can you tell if they are seizing?

Answer 12

Check the EEG

Question 13

How is refractory status epilepticus treated?

Answer 13

High dose BZD
- Midazolam bolus and infusion
Propofol infusion
Phenobarbital/Pentobarbital coma

Question 14

What is a phenobarbital/pentobarbital coma?

Answer 14

A complete brain shutdown, suppresses the sensory cortex
Only use in intubated!!
Lots and lots of ADRs!! (Hypotension, respiratory depression, lethargy, nystagmus, thrombocytopenia, immune suppression, decreased GI function)

Question 15

How is super refractory status epilepticus treated?

Answer 15

Ketamine infusion

Question 16

What agents should be tapered off after status epilepticus is acutely controlled?

Answer 16

1. Phenobarbitals, pentobarbitals, propofol (often results in need for pressors)
2. Midazolam (accumulates in fatty tissue)