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27.6 Status epilepticus

27.6.1 General information

Key concepts
● definition: Sz > 5 mins, or persistent Sz after 1 st & 2 nd line AEDs
● morbidity and mortality are high in untreated status epilepticus (SE)
● most common etiology: patient with known Sz disorder with low AED levels
● de novo SE in acute illness is considered a manifestation of the illness which should be treated at
the same time as the SE
● see ▶ Table 2 7 .5 for treatment measures

▶ Definition. A seizure lasting > 5 minutes or persistent seizure activity after sequential administra-
tion of appropriate first and second-line AEDs.31

27 ▶ Features important to management:

● 61% of seizures that persist > 5 mins will continue > 1 hour32

Table 27.5 Summary of initial steps for status epilepticus (adults and children > 1 3 kg; see text for details)40
ABC’s. Start O2 . Turn patient on their side. Check VS. Do a neuro exam
Monitor/labs: Pulse oximetry. EKG/telemetry. ✔ Fingerstick glucose.
Blood tests (do not wait for results to begin ℞):✔ electrolytes, ✔ CBC, ✔ ABG, ✔ AED levels, ✔ LFTs, ✔ Mg + + , ✔
Ca + + , ✔ head CT
Large bore IV X 2 . Start IV fluids
● thiamine 1 0 0 mg IV and/or 50 ml of 50 % dextrose (if needed based on fingerstick glucose)
First-line AED:
● lorazepam (Ativan®) 4 mg IV for adults, 2 mg IV for children > 1 3 kg @ < 2 mg/min
OR
● midazolam (Versed®) 1 0 mg IM for adults, 5 mg IM for children > 1 3 kg OR (if no IV access or midazolam
injections not available)
● diazepam can be given rectally in Diastat® gel formulation (0 .2 –0 .5 mg/kg)
Repeat loading dose of benzodiazepine if necessary
Second-line AED: given with failure of (or simultaneously with administration of) repeat dose of benzodiazepine
● fosphenytoin: 1 5–2 0 mg PE/kg IV @ < 1 50 mg PE/min (preferred drug: faster infusion rate, less irritation)
OR
● phenytoin: 1 5–2 0 mg/kg IV @ < 50 mg/min (less expensive) If no response to loading dose, an additional
1 0 mg/kg IV may be given after 2 0 min.
NB: following infusion rate guidelines is imperative. Significant cardiovascular risk is associated with rapid
infusion of phenytoin/fosphenytoin.
✔ phenytoin level ≈ 1 0 min after PHT loading dose; repeat 1 0 min later additional dose if required
Alternative second-line AEDs:
● sodium valproate: 2 0 –30 mg/kg IV bolus (max rate: 1 0 0 mg/min)—has been shown to be equal or superior to
phenytoin in a few small studies
OR
● phenobarbital: 2 0 mg/kg IV (start infusing @ 50 –1 0 0 mg/min)—commonly used 2 nd or 3rd line AED. A repeat
dose of 2 5–30 mg/kg can be given 1 0 min after first dose
OR
● Levetiracetam (Keppra®): 2 0 mg/kg IV bolus of over 1 5 minutes – evidence for Keppra as a first or second line
drug is less clear
If seizures continue > 30 mins and are refractory to 1 st and 2 nd line AEDs: intubate in ICU and begin continuous
infusion therapy (CIT) of:
● Midazolam: 0 .2 mg/kg IV loading dose followed by 0 .2 –0 .6 mg/kg/hr
OR
● Propofol: 2 mg/kg IV loading dose followed by 2 –5 mg/kg/hr

If Sz persist, ensure that correctable conditions have been ruled-out and/or treated
Novel therapeutic options (not systematically studied): shock therapy…
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Special Types of Seizures 487

● in patients with no prior Sz history, status epilepticus (SE) is usually a manifestation of illness-
related cortical irritation or injury31 and treatment of the underlying disorder (in addition to treat-
ing the SE) is critical
● a relapse of Sz in a patient with a known Sz disorder and subtherapeutic AED levels usually
responds to a bolus of the maintenance AEDs. However, SE should be treated by the standard
protocol31
● most cases of convulsive status in adults start as partial seizures that generalize secondarily
● the choice of 1st and 2nd-line AEDs is arbitrary, dose31 and starting treatment in < 30 minutes33
are more important determinants of success in aborting SE

27.6.2 Types of status epilepticus

See reference.34
● generalized status
1. convulsive (tonic-clonic, tonic-clonic-tonic, or clonic): generalized convulsive tonic-clonic sta-
tus epilepticus (SE) is the most frequent type.35 A medical emergency
2. absence (note: in status, this may present in twilight state)
3. secondarily generalized: accounts for ≈ 75% of generalized SE
4. myoclonic 27
5. atonic (drop attack): especially in Lennox-Gastaut syndrome (p. 461)
● partial status (usually related to an anatomic abnormality)
1. simple (AKA epilepsy partialis continua)
2. complex (note: in status, this may present in twilight state) most often from frontal lobe focus.
Urgent treatment is required (several case reports of permanent deficits following this)
3. secondarily generalized
● non-convulsive SE
1. benign variants (typical absence SE, complex partial SE)
2. electrical SE during sleep
3. atypical absence SE
4. tonic SE (associated with learning disability in children), SE in coma

Alternatively, SE can be broken down as follows:

● with prominent motor effects
● without prominent motor effects
● boundary syndromes (syndromes which combine encephalopathy, behavioral disturbances, delir-
ium, or psychosis with SE-like EEG findings)

27.6.3 Epidemiology
Incidence is ≈ 150,000 new cases/year in the U.S. in the outpatient setting.31 Most cases occur in
young children (among children, 73% were < 5 yrs old36); the next most affected group is
s first seizure.35 One out of six patients
patients > 60 yrs of age. In > 50% of cases, SE is the patient’
presenting with a first time seizure will present in SE.

27.6.4 Etiologies
Most common causes: low level of AED (34%), remote symptomatic cause (24%), cerebrovascular
accident (22%), metabolic disturbances (15%), and hypoxia (13%).
A more comprehensive list:
1. a patient with a known seizure disorder having low AED levels for any reason (non-compliance,
intercurrent infection preventing PO intake of meds, drug-drug interactions → lowering effec-
tiveness of AEDs…)
2. febrile seizures: a common precipitator in young patients. 5–6% of patients presenting with SE
have a history of prior febrile seizures
3. stroke: the most commonly identified cause in the elderly
4. CNS infection: in children, most are bacterial, the most common organisms were H. influenza
and S. pneumoniae
5. idiopathic: accounts for ≈ one-third (in children, usually associated with fever)
6. epilepsy: is present or is subsequently diagnosed in ≈ 50% of patients presenting with SE. About
10% of adults ultimately diagnosed as having epilepsy will present in SE
7. electrolyte imbalance: hyponatremia (most common in children, usually due to water intoxica-
tion36), hypoglycemia, hypocalcemia, uremia, hypomagnesemia…
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488 Seizures

8. illicit drug intoxication: especially cocaine, amphetamines

9. precipitous drug withdrawal: barbiturates, benzodiazepines, alcohol, or narcotics
10. proconvulsant drugs, including: β-lactam antibiotics (penicillins, cephalosporins), certain anti-
depressants (bupropion), clonazapine, bronchodilators, immunosuppressants
11. traumatic brain injury: acute as well as old
12. hypoxia/ischemia
13. tumor

In children < 1 yr of age, 75% had an acute cause: 28% were secondary to CNS infection, 30% due to
electrolyte disorders, 19% associated with fever.36 In adults, a structural lesion is more likely. In an
adult, the most common cause of SE is subtherapeutic AED levels in a patient with a known seizure
disorder.

27.6.5 Morbidity and mortality from SE

Outcomes are related to underlying cause and duration of SE. Mean duration of SE in patients with-
out neurologic sequelae is 1.5 hrs (therefore, proceed to pentobarbital anesthesia before ≈ 1 hour of
SE). Recent mortality: < 10–12% (only ≈ 2% of deaths are directly attributable to SE or its complica-
27 tions; the rest are due to the underlying process producing the SE). Mortality is lowest amongst chil-
dren (≈ 6%36), patients with SE related to subtherapeutic AEDs, and patients with unprovoked SE.37
The highest mortality occurs in elderly patients and those with SE resulting from anoxia or stroke.37
1% of patients die during the episode itself.
Morbidity and mortality is due to38:
1. CNS injury from repetitive electric discharges: irreversible changes begin to appear in neurons
after as little as 20 minutes of convulsive activity. Cell death is very common after 60 mins
2. systemic stress from the seizure (cardiac, respiratory, renal, metabolic)
3. CNS damage by the acute insult that provoked the SE

27.6.6 Treatment
General treatment measures for status epilepticus
Treatment success, like morbidity/mortality, may be time-dependent. One review showed that first-
line AED therapy aborted SE in 60% of patients if initiated within the first 30 minutes, and efficacy
decreased as seizure duration increased.39 As such, treatment should be initiated as soon as possible
and should be directed at stabilizing the patient, stopping the seizure, identifying the cause (deter-
mining if there is an acute insult to the brain), and, if possible, also treating the underlying process.
Treatment often must be initiated prior to the availability of test results to confirm the diagnosis and
may even be initiated in the pre-hospital setting.
1. “ABC’ s”
a) Airway: oral airway if feasible. Turn patient on their side to avoid aspiration
b) Breathing: O2 by nasal cannula or bag-valve-mask. Consider intubation if respirations com-
promised or if seizure persists > 30 min
c) Circulation: CPR if needed. Large bore proximal IV access (2 if possible: 1 for phenytoin (PHT)
(Dilantin®), not necessary if fosphenytoin is available): start with NS KVO
2. Simultaneous with ABCs, AEDs should be prepared and/or given if SE suspected
3. neurologic exam
4. monitor: EKG & baseline vital signs. Pulse oximeter. Frequent blood pressure checks
5. bloodwork: STAT capillary blood (fingerstick) glucose (to R/O hypoglycemia), electrolytes
(including glucose), CBC, LFTs, Mg + + , Ca + + , AED levels, ABG
6. head CT (usually without contrast)
7. correct any electrolyte imbalance (SE due to electrolyte imbalance responds more readily to cor-
rection than to AEDs36)
8. if CNS infection is a major consideration, perform LP for CSF analysis (especially in febrile chil-
dren) unless contraindicated (p. 1598). WBC pleocytosis up to 80 × 106/L can occur following SE
(benign postictal pleocytosis), and these patients should be treated with antibiotics until infec-
tion can be ruled out by negative cultures
9. general meds for unknown patient:
a) glucose:
● in patients with poor nutrition (e.g. alcoholics): giving glucose in thiamine deficiency can
precipitate Wernicke’ s encephalopathy (p. 221) ∴ prior to glucose bolus give thiamine 50–
100 mg IV
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Special Types of Seizures 489

● if fingerstick glucose can be obtained immediately and it shows hypoglycemia, or if no fin-

gerstick glucose can be done: give 25–50 ml of D50 IV push for adults (2 ml/kg of 25% glu-
cose for peds). If at all possible, draw blood for definitive serum glucose first
b) naloxone (Narcan®) 0.4 mg IVP (in case of narcotics)
c) ± bicarbonate to counter acidosis (1–2 amps depending on length of seizure)
d) for neonate < 2 years: consider pyridoxine 100 mg IV push (pyridoxine-dependent seizures
constitute a rare autosomal recessive condition that generally presents in the early neonatal
period32)
10. administer specific anticonvulsants for seizures lasting > 5- 10 mins (see below)
11. EEG monitor if possible
12. if paralytics are used (e.g. to intubate), use short acting agents and be aware that muscle paraly-
sis alone may stop visible seizure manifestations, but does not stop the electrical seizure activity
in the brain, which can lead to permanent neurologic damage if prolonged (see above).

Medications for generalized convulsive status epilepticus

General information
There are no randomized trials for refractory status epilepticus, although there is published data
regarding specific treatment options. Numerous protocols exist. ▶ Table 27.5 shows a summary of 27
medications for a status epilepticus protocol that is outlined in further detail below (adapted31,34,40,41).
“Peds dosing” refers to patients < 40 kg or approximately 12 yrs of age. Rapid treatment is indicated as
delays are associated with neuronal injury and reduced response to medications.

Prehospital phase
1. impending SE: may be heralded by a crescendo in Sz. A 1–3 d course of lorazepam may preempt
the development of SE
2. SE treatment may be initiated in the home setting with buccal midazolam or rectal diazepam

Hospital phase
Start IV drugs at half the maximal rate, and titrate up to maximal rate if VS stable.
1. First line drugs
a) benzodiazepine42 (main side effect: respiratory depression in ≈ 12%; be prepared to intubate).
Onset of action is rapid (1–2 mins):
● lorazepam (Ativan®) 4 mg IV for adults, 2 mg IV for children @ < 2 mg/min
● OR midazolam (Versed®) 10 mg IM for adults, 5 mg IM for children > 13 kg. Repeat dose of
benzodiazepine if necessary after 10 min.
● If no IV access or if midazolam injections not available, diazepam can be given rectally in
Diastat® gel formulation (0.2–0.5 mg/kg)
2. If seizures persist after first dose of benzodiazepine, initiate second line agent in a different IV.
a) load with fosphenytoin (Cerebyx®) or phenytoin (Dilantin®) as listed below. Do not worry
about acutely overdosing, but do follow dosing rates, monitor BP for hypotension and EKG for
arrhythmias. After giving the following loading dose, start on maintenance. Fosphenytoin has
the advantage of being less irritating and able to infuse at a faster rate, but phenytoin is less
expensive and does not need to be metabolized.
● fosphenytoin: 15–20 mg PE/kg IV @ 150 mg PE/min
● OR phenytoin: 15–20 mg/kg IV @ 50 mg/min
- if no response to loading dose, an additional 10 mg/kg IV may be given after 20 min.
- if pt is on PHT and a recent level is known: a rule of thumb is giving 0.74 mg/kg to an adult
raises the level by ≈ 1 mcg/ml
- if on PHT and level not known: adult: give 500 mg @ < 50 mg/min
b) There are several good alternatives to fosphenytoin/phenytoin as second-line AEDs:
● Sodium valproate: 20–30 mg/kg IV bolus (max rate: 100 mg/min)—has been shown to be
equal or superior to phenytoin in a few small studies
● Phenobarbital: 20 mg/kg IV (start infusing @ 50–100 mg/min) – commonly used 2nd or 3rd
line AED. A repeat dose of 25–30 mg/kg can be given 10 min after first dose.
● Levetiracetam (Keppra®): 20 mg/kg IV bolus of over 15 minutes – evidence for Keppra as a
first or second line drug is less clear
3. Traditionally, a third line agent was given prior to continuous infusion therapy (CIT); however, it
was successful in only 7%.42 As such, most new protocols proceed directly to anesthetic adminis-
tration. If seizures are continuing after above therapies have been administered (15–30 min after
initial presentation), begin CIT as follows:
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490 Seizures

● Midazolam: 0.2 mg/kg IV loading dose followed by 0.2–0.6 mg/kg/hr

● OR Propofol: 2 mg/kg IV loading dose followed by 2–10 mg/kg/hr
4. At this time, lab results and tests should be available. Ensure that all reversible etiologies have
been addressed and that a CT head has been performed.
5. Pentobarbital is often reserved for SE that is refractory to all of the above interventions. If neces-
sary, pentobarbital is administered as follows:
● Pentobarbital: 5 mg/kg IV followed by 1–5 mg/kg/hr
6. While some practitioners will try additional drugs (carbamazepine, oxcarbazepine, topiramate,
levetiracetam, lamotrigine, gabapentin), these are likely to be of limited utility.
7. Experimental interventions include: lidocaine infusion, inhalational anesthesia, direct brain sti-
mulation, transcranial magnetic stimulation, electroconvulsive therapy (shock therapy), surgical
intervention if a seizure focus is identified

Remember: Paralytics stop the visible manifestations of the seizure and they may be useful for intu-
bation and/or in order to obtain head imaging; however, they do not stop the abnormal electrical
brain activity or the neurological damage that results.

27 Efficacy of drug therapy

Studies vary widely, but it appears that approximately 2/3 of patients will respond to initial therapy
with the other 1/3 progressing to refractory SE.40

Medications to avoid in status epilepticus

1. narcotics
2. phenothiazines: including promethazine (Phenergan®)
3. neuromuscular blocking agents in the absence of AED therapy: seizures may continue and cause
neurologic injury but would not be clinically evident

27.6.7 Medications for non-convulsive status epilepticus

In non-convulsive status epilepticus, the first and second line AEDs listed in ▶ Table 27.5 should be uti-
lized. However, many practitioners avoid escalating to the anesthetic options (CIT, pentobarbital), instead
opting for trials of additional AEDs first (carbamazepine, oxcarbazepine, topiramate, lamotrigine, etc).

27.6.8 Miscellaneous status epilepticus

Myoclonic status
Treatment: valproic acid (drug of choice). Place NG, give 20 mg/kg per NG loading dose. Maintenance:
40 mg/kg/d divided.
Can add lorazepam (Ativan®) or clonazepam (Klonopin®) to help with acute control.

Absence status epilepticus

Almost always responds to diazepam.

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