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Pharmacotherapy and
Management of Status Epileptics
Definition of Status Epilepticus(Lowenstein DH. 1999)
• Traditionally defined as continuous, unremitting
seizure lasting longer than 30 minutes, or
recurrent seizures without regaining
consciousness between seizures for greater than
30 minutes.
• Newer literature and common neurology practice
usually accepts 5 minutes or longer as definition
for status epilepticus.
ETIOLOGIEs
Antiepileptic drug (AED)
noncompliance/insufficien
t dosing 20%
CNS infection 5%
Old brain injury 15% Cerebral tumor 5%
Acute vascular injury 15% Acute Trauma 5%
Alcohol related 10% Drug toxicity < 5%
Metabolic/electrolyte
disturbances 10%
Global hypoxic injury < 5%
Unknown/cryptogenic 10% Idiopathic epilepsy < 5%
TIME IS BRAIN
• Status should always be
treated as an emergency and
be treated promptly!
Types of Seizures
• Seizures can manifest as motor, sensory, or cognitive
dysfunction
• Classification of seizures
– Partial – seizures localized to an area of the brain resulting
in a corresponding localized dysfunction. Often described by
presence of absence of automatisms (ie lip smacking, jaw
mvmts, swallowing, fumbling with nearby objects) or
repeated subconscious or involuntary movements .
• Simple (w/o impairment of consciousness)
• Complex (w/ impairment of consciousness)
**Please note partial seizures can develop into secondarily
generalized seizures as abnormal electrical activity
spreads through the brain
Classification of Seizures
- Generalized seizures are characterized by the resulting
dysfunction
-Absence (loss of consciousness with no motor dysfunction)
-Myoclonic (bilaterally synchronous, arrythmic jerking)
-Clonic (repetitive and rhythmic motor movement)
-Tonic (extension of the arms, legs, & trunk)
-Tonic-clonic (extension of the arms, legs, & trunk followed
by repetitive, rhythmic movement)
-Atonic (aka drop-attack, absence of motor movement)
[Parillo & Dellinger, 2008]
Frontal Seizure with vocalizations, and hypermotor
activity
Partial seizure w/ secondary generalization
Types of Status Epilepticus
• CONVULSIVE
– Generalized (Most common presentation of SE)
• Myoclonic
• Clonic
• Tonic
• Tonic-Clonic
– Partial
• Simple
• Complex
• Secondarily Generalized
Types of Status Epilepticus
• SUBTLE CONVULSIVE
– About 30% SE population
– Longer duration & more difficult to treat
– Clinical features:
• Continuous rhythmic subtle motor phenomena
• Facial twitching, nystagmoid eye jerks
• Subtle twitching of extremities
• Cognitive impairment (altered awareness)
• Head or eye deviation
• Automatisms
Possible Findings in Convulsive Status
• Generalized convulsions w/ bilaterally
symmetric myoclonic, tonic, clonic, or tonic-
clonic movements
• Convulsions on 1 side of body (not
symmetric) with repetitive involuntary
movements
Possible findings in Non-convulsive Status
Behavioral, cognitive, or sensory findings:
– Agitation, aggression, amnesia, aphasia muteness,
catatonia, coma, confusion, delerium, delusions,
hallucinations, laughter, perseveration, singing,
psychosis
Autonomic:
• Abdominal sensation, apnea, hyperventilation, brady
or tachyarrythmia, flushing, miosis, mydriasis,
hiccups, nausea, vomiting
Motor:
– Automatisms, dystonic posturing, eye blinking, eye
deviation, facial twitching, finger twitching
Responsiveness of Treatment of SE
• Treatment with 1st
line therapy within 30
minutes of onset stopped status in 80% of
patients
• Treatment with first line therapy started
>/= 2 hrs after onset stopped status in 40%
of patients
Monitoring For Status in the ICU……
• Continuous EEG [cEEG] (continuous EEG 24 hr
order in WIZ) is ideal for capturing seizure activity
• Using cEEG captures 56% of seizures in first hour
and 88% of seizures in first 24 hrs
• Note: some factors which may limit obtaining
and/or interpreting EEG include head bandages,
delerium w/ mvmts, sweating, and aritifact from
electrical interference of mechanical devices ie
vent, ECT, dialysis. Also availability of EEGs in the
hospital plays a role
INITIAL MEDICAL MANAGEMENT
• ABCS (airway, breathing, circulation)
• Obtain IV access (2 sites preferably)
• Check finger stick glucose
• Give thiamine 100mg IV prior to Dextrose D50W 50ml
IV if low or unknown glucose
• Continuous monitoring (ECG, BP, HR, oxygen)
• Send stat labs (CBC, BMP, LFTs, Ca, Mg, PO4,
troponins, ABGs, AED lvls if on seizure meds, tox
screen (urine, blood), Hcg if pregnancy possible
• Continuous EEG monitoring if possible
Obtain history & exam
• History of epilepsy & AED use, structural brain
lesion (stroke, intracranial hemorrhage, tumor),
head trauma, meningitis, social history (illegal
drug or ETOH use), pregnancy
• Medical History including medications
• Seizure onset & duration, description of seizure
• Full neurologic exam including mental status,
cranial nerves, motor exam, sensory exam,
reflexes, cerebellar testing
Treatment of Convulsive SE
First Line Agents:
•▪Lorazepam Load IV 0.1mg/kg up to 4mg (2mg/min)
•▪Midazolam Load IM 0.2mg/kg up to 10mg IM
•▪Diazepam Load 0.2mg/kg (20mg rectally or 10mg IV)
Second-Line Agents
•▪Fosphenytoin 20mg/kg infused at a rate of 150mg/min
•▪Valproate 20-40mg/kg infused at a rate of 6mg/kg/min
•▪Levetiracetam 1500-4000mg infuse 500mg/min
•▪Lacosamide 400mg IV infuse over 5 mins
•▪Phenobarbital 20mg/kg IV infuse 60mg/min
• Initial Treatment
• ▪Lorazepam Load IV 0.1mg/kg up to 4mg (2mg/min)
• ▪Midazolam Load IM 0.2mg/kg up to 10mg IM
• ▪Diazepam Load 0.2mg/kg (20mg rectally or 10mg IV)
• Second-Line Agents
• ▪Fosphenytoin 20mg/kg infused at a rate of 150mg/min
• ▪Valproate 20-40mg/kg infused at a rate of 6mg/kg/min
Treatment of Convulsive SE
Third Line Agents
• ▪Midazolam infusion (Hypotension, withdrawl seizures)
• ▪Propofol infusion (Hypotension, propofol infusion syndrome)
• ▪Pentobarbital (Ileus, metabolic acidosis, thrombocytopenia,
immunosuppression)
• ▪Ketamine infusion (Hypertension, possible rise in ICP)
• ▪Etomidate infusion (Adrenal insufficiency, non-epileptic
myoclonus)
• ▪Lidocaine administration every 5 minutes (cardiac
arrhythmia)
Management on Bedside
 Treatment of an Ongoing Seizure
1. Keep calm.
1. It is likely that others in the room are reacting with fear or
panic.
2. Ask family members to leave the room.
3. Tell them you will speak with them as soon as the
situation is evaluated and under control.
2. Have one or two people maintain the patient in a lateral
decubitus position.
3. Administer oxygen by nasal cannula or face mask.
4. Watch and wait for 2 minutes. A majority of seizures will
stop spontaneously within a short time..
 Check the finger stick glucose level.
 Make sure there are two IV setups available, at least one
with 0.9% normal saline (NS). If the patient has no IV access,
start an IV line. IV insertion and blood drawing will be much
easier.
 Draw Diazepam 5mg IV slowly.
 Elicit any further history not obtained initially.
 Is this a first-ever seizure? Is the patient on anticonvulsants?
What is the patient’s admitting diagnosis? Is the patient
diabetic? Has the patient been febrile in the last 24 hours? Ask
for the chart to be brought to the bedside.
 Observe the seizure type.
 Order the following blood tests: (CBC), electrolytes, glucose,
magnesium (Mg), calcium (Ca), EtOH level, toxicology screen, and
anticonvulsant level (if applicable).
 If the patient is hypoglycemic, give glucose (50 ml of D50W). If
there is any history or suspicion of alcoholism, administer thiamine
100 mg by slow, direct injection over 3 to 5 minutes. If
hypoglycemia is the cause of the seizure, the seizure should stop,
and the patient should wake up soon after the glucose
administration.
 An Ambu bag with face mask should be at the bedside
because benzodiazepines can cause respiratory depression.
Summary
• Status is an emergency & requires
immediate treatment
• Remember sometimes status seizures are
not obvious, symptoms can be very subtle
or may only present as altered mental
status
• If you are concerned about seizures, consult
neurology right away for continuous EEG
monitoring
References
• Lowenstein DH. Status epilepticus: an overview of the clinical problem.
Epilepsia 1999; 40(Suppl 1); discussion S21-22
• Jordan KG. Status epilepticus. A perspective from the neuroscience intensive
care unit. Neurosurg Clin N Am. 1994;5:671-686
• Allredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam,
and placebo fo the treatment of out of hospital status epilepticus. N Engl J Med
2001; 345(9):631-637.
• Towne AR, Waterhouse EJ, Boggs JG, Garnett LK, Brown AJ, Smith JR Jr,
DeLorenzo RJ. Presence of nonconvulsive status epilepticus in comatose
patients. Neurology 2000;54:340-345
• Parillo JE & Dellinger RP. (2008). Critical Care Medicine: Principles of Diagnosis
and Management in the Adult. St Louis, MO: Mosby Elsevier
• Sutter, R, Stevens R, and Kaplan P. Continuous Electroencephalographic
Monitoring in Critically Ill Patients: Indications, Limitations, and Strategies.
CCM Journal. 2013, 41(4) 1124-1132

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status epilepticus

  • 2. Definition of Status Epilepticus(Lowenstein DH. 1999) • Traditionally defined as continuous, unremitting seizure lasting longer than 30 minutes, or recurrent seizures without regaining consciousness between seizures for greater than 30 minutes. • Newer literature and common neurology practice usually accepts 5 minutes or longer as definition for status epilepticus.
  • 3. ETIOLOGIEs Antiepileptic drug (AED) noncompliance/insufficien t dosing 20% CNS infection 5% Old brain injury 15% Cerebral tumor 5% Acute vascular injury 15% Acute Trauma 5% Alcohol related 10% Drug toxicity < 5% Metabolic/electrolyte disturbances 10% Global hypoxic injury < 5% Unknown/cryptogenic 10% Idiopathic epilepsy < 5%
  • 4. TIME IS BRAIN • Status should always be treated as an emergency and be treated promptly!
  • 5. Types of Seizures • Seizures can manifest as motor, sensory, or cognitive dysfunction • Classification of seizures – Partial – seizures localized to an area of the brain resulting in a corresponding localized dysfunction. Often described by presence of absence of automatisms (ie lip smacking, jaw mvmts, swallowing, fumbling with nearby objects) or repeated subconscious or involuntary movements . • Simple (w/o impairment of consciousness) • Complex (w/ impairment of consciousness) **Please note partial seizures can develop into secondarily generalized seizures as abnormal electrical activity spreads through the brain
  • 6. Classification of Seizures - Generalized seizures are characterized by the resulting dysfunction -Absence (loss of consciousness with no motor dysfunction) -Myoclonic (bilaterally synchronous, arrythmic jerking) -Clonic (repetitive and rhythmic motor movement) -Tonic (extension of the arms, legs, & trunk) -Tonic-clonic (extension of the arms, legs, & trunk followed by repetitive, rhythmic movement) -Atonic (aka drop-attack, absence of motor movement) [Parillo & Dellinger, 2008]
  • 7. Frontal Seizure with vocalizations, and hypermotor activity
  • 8. Partial seizure w/ secondary generalization
  • 9. Types of Status Epilepticus • CONVULSIVE – Generalized (Most common presentation of SE) • Myoclonic • Clonic • Tonic • Tonic-Clonic – Partial • Simple • Complex • Secondarily Generalized
  • 10. Types of Status Epilepticus • SUBTLE CONVULSIVE – About 30% SE population – Longer duration & more difficult to treat – Clinical features: • Continuous rhythmic subtle motor phenomena • Facial twitching, nystagmoid eye jerks • Subtle twitching of extremities • Cognitive impairment (altered awareness) • Head or eye deviation • Automatisms
  • 11. Possible Findings in Convulsive Status • Generalized convulsions w/ bilaterally symmetric myoclonic, tonic, clonic, or tonic- clonic movements • Convulsions on 1 side of body (not symmetric) with repetitive involuntary movements
  • 12. Possible findings in Non-convulsive Status Behavioral, cognitive, or sensory findings: – Agitation, aggression, amnesia, aphasia muteness, catatonia, coma, confusion, delerium, delusions, hallucinations, laughter, perseveration, singing, psychosis Autonomic: • Abdominal sensation, apnea, hyperventilation, brady or tachyarrythmia, flushing, miosis, mydriasis, hiccups, nausea, vomiting Motor: – Automatisms, dystonic posturing, eye blinking, eye deviation, facial twitching, finger twitching
  • 13. Responsiveness of Treatment of SE • Treatment with 1st line therapy within 30 minutes of onset stopped status in 80% of patients • Treatment with first line therapy started >/= 2 hrs after onset stopped status in 40% of patients
  • 14. Monitoring For Status in the ICU…… • Continuous EEG [cEEG] (continuous EEG 24 hr order in WIZ) is ideal for capturing seizure activity • Using cEEG captures 56% of seizures in first hour and 88% of seizures in first 24 hrs • Note: some factors which may limit obtaining and/or interpreting EEG include head bandages, delerium w/ mvmts, sweating, and aritifact from electrical interference of mechanical devices ie vent, ECT, dialysis. Also availability of EEGs in the hospital plays a role
  • 15. INITIAL MEDICAL MANAGEMENT • ABCS (airway, breathing, circulation) • Obtain IV access (2 sites preferably) • Check finger stick glucose • Give thiamine 100mg IV prior to Dextrose D50W 50ml IV if low or unknown glucose • Continuous monitoring (ECG, BP, HR, oxygen) • Send stat labs (CBC, BMP, LFTs, Ca, Mg, PO4, troponins, ABGs, AED lvls if on seizure meds, tox screen (urine, blood), Hcg if pregnancy possible • Continuous EEG monitoring if possible
  • 16. Obtain history & exam • History of epilepsy & AED use, structural brain lesion (stroke, intracranial hemorrhage, tumor), head trauma, meningitis, social history (illegal drug or ETOH use), pregnancy • Medical History including medications • Seizure onset & duration, description of seizure • Full neurologic exam including mental status, cranial nerves, motor exam, sensory exam, reflexes, cerebellar testing
  • 17. Treatment of Convulsive SE First Line Agents: •▪Lorazepam Load IV 0.1mg/kg up to 4mg (2mg/min) •▪Midazolam Load IM 0.2mg/kg up to 10mg IM •▪Diazepam Load 0.2mg/kg (20mg rectally or 10mg IV) Second-Line Agents •▪Fosphenytoin 20mg/kg infused at a rate of 150mg/min •▪Valproate 20-40mg/kg infused at a rate of 6mg/kg/min •▪Levetiracetam 1500-4000mg infuse 500mg/min •▪Lacosamide 400mg IV infuse over 5 mins •▪Phenobarbital 20mg/kg IV infuse 60mg/min
  • 18. • Initial Treatment • ▪Lorazepam Load IV 0.1mg/kg up to 4mg (2mg/min) • ▪Midazolam Load IM 0.2mg/kg up to 10mg IM • ▪Diazepam Load 0.2mg/kg (20mg rectally or 10mg IV) • Second-Line Agents • ▪Fosphenytoin 20mg/kg infused at a rate of 150mg/min • ▪Valproate 20-40mg/kg infused at a rate of 6mg/kg/min
  • 19. Treatment of Convulsive SE Third Line Agents • ▪Midazolam infusion (Hypotension, withdrawl seizures) • ▪Propofol infusion (Hypotension, propofol infusion syndrome) • ▪Pentobarbital (Ileus, metabolic acidosis, thrombocytopenia, immunosuppression) • ▪Ketamine infusion (Hypertension, possible rise in ICP) • ▪Etomidate infusion (Adrenal insufficiency, non-epileptic myoclonus) • ▪Lidocaine administration every 5 minutes (cardiac arrhythmia)
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  • 22. Management on Bedside  Treatment of an Ongoing Seizure 1. Keep calm. 1. It is likely that others in the room are reacting with fear or panic. 2. Ask family members to leave the room. 3. Tell them you will speak with them as soon as the situation is evaluated and under control. 2. Have one or two people maintain the patient in a lateral decubitus position. 3. Administer oxygen by nasal cannula or face mask. 4. Watch and wait for 2 minutes. A majority of seizures will stop spontaneously within a short time..
  • 23.  Check the finger stick glucose level.  Make sure there are two IV setups available, at least one with 0.9% normal saline (NS). If the patient has no IV access, start an IV line. IV insertion and blood drawing will be much easier.  Draw Diazepam 5mg IV slowly.  Elicit any further history not obtained initially.  Is this a first-ever seizure? Is the patient on anticonvulsants? What is the patient’s admitting diagnosis? Is the patient diabetic? Has the patient been febrile in the last 24 hours? Ask for the chart to be brought to the bedside.  Observe the seizure type.
  • 24.  Order the following blood tests: (CBC), electrolytes, glucose, magnesium (Mg), calcium (Ca), EtOH level, toxicology screen, and anticonvulsant level (if applicable).  If the patient is hypoglycemic, give glucose (50 ml of D50W). If there is any history or suspicion of alcoholism, administer thiamine 100 mg by slow, direct injection over 3 to 5 minutes. If hypoglycemia is the cause of the seizure, the seizure should stop, and the patient should wake up soon after the glucose administration.  An Ambu bag with face mask should be at the bedside because benzodiazepines can cause respiratory depression.
  • 25. Summary • Status is an emergency & requires immediate treatment • Remember sometimes status seizures are not obvious, symptoms can be very subtle or may only present as altered mental status • If you are concerned about seizures, consult neurology right away for continuous EEG monitoring
  • 26. References • Lowenstein DH. Status epilepticus: an overview of the clinical problem. Epilepsia 1999; 40(Suppl 1); discussion S21-22 • Jordan KG. Status epilepticus. A perspective from the neuroscience intensive care unit. Neurosurg Clin N Am. 1994;5:671-686 • Allredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo fo the treatment of out of hospital status epilepticus. N Engl J Med 2001; 345(9):631-637. • Towne AR, Waterhouse EJ, Boggs JG, Garnett LK, Brown AJ, Smith JR Jr, DeLorenzo RJ. Presence of nonconvulsive status epilepticus in comatose patients. Neurology 2000;54:340-345 • Parillo JE & Dellinger RP. (2008). Critical Care Medicine: Principles of Diagnosis and Management in the Adult. St Louis, MO: Mosby Elsevier • Sutter, R, Stevens R, and Kaplan P. Continuous Electroencephalographic Monitoring in Critically Ill Patients: Indications, Limitations, and Strategies. CCM Journal. 2013, 41(4) 1124-1132