Convulsive Status Epilepticus in Adults - Management - UpToDate

24/12/21 13:01 Convulsive status epilepticus in adults: Management - UpToDate
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Convulsive status epilepticus in adults: Management

Author: Frank W Drislane, MD
Section Editors: Paul Garcia, MD, Jonathan A Edlow, MD, FACEP, Alejandro A Rabinstein, MD
Deputy Editor: John F Dashe, MD, PhD
All topics are updated as new evidence becomes available and our peer review process is complete.
Literature review current through: Nov 2021. | This topic last updated: Dec 09, 2021.
INTRODUCTION
Status epilepticus is a medical and neurologic emergency that requires prompt evaluation and
treatment. The rapid evaluation and treatment of convulsive status epilepticus is discussed
below.
The definition, classification, clinical features, and diagnosis of convulsive status epilepticus in
adults are reviewed separately. (See "Convulsive status epilepticus in adults: Classification,
clinical features, and diagnosis".)
Nonconvulsive status epilepticus and the diagnosis and management of status epilepticus in
children are discussed elsewhere. (See "Nonconvulsive status epilepticus: Classification, clinical
features, and diagnosis" and "Clinical features and complications of status epilepticus in
children" and "Management of convulsive status epilepticus in children".)
RAPID RECOGNITION OF STATUS EPILEPTICUS
● Diagnosis – The diagnosis of convulsive status is clinical and is confirmed by verifying the
presence of either an unremitting generalized convulsive seizure lasting longer than five
minutes or frequent motor seizures without an interictal return to the baseline level of
consciousness.
Patients with generalized motor seizures that are frequent or separated by a period of
significantly impaired consciousness (ie, status epilepticus) or who are medically unstable
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require immediate assessment and treatment in an acute care setting (emergency

department or intensive care unit). (See "Convulsive status epilepticus in adults:
Classification, clinical features, and diagnosis", section on 'Definition of status epilepticus'.)
● Differential diagnosis – Few other conditions appear similar to generalized convulsive

status epilepticus. Focal motor and myoclonic status epilepticus may be more difficult to
distinguish from other conditions. The main considerations in the differential are:
• Psychogenic status epilepticus

• Encephalopathies with unresponsiveness and myoclonus
• Movement disorders, such as tremors and dystonias
The differential diagnosis of convulsive status epilepticus is reviewed in greater detail

separately. (See "Convulsive status epilepticus in adults: Classification, clinical features,
and diagnosis", section on 'Differential diagnosis'.)
● Speed – Treatment of status epilepticus is time sensitive. One small study found that
creating and implementing a "status epilepticus alert" (similar in concept to a "code
stroke" or "code ST-elevation myocardial infarction") reduced the time to administration of
a nonbenzodiazepine antiseizure medication from 58 minutes to 22 minutes [1].
Initial management involves rapid assessment and supportive treatment; urgent

pharmacologic therapy with a benzodiazepine; and urgent therapy that achieves long-term
control using a nonbenzodiazepine antiseizure medication ( algorithm 1).
URGENT FOCUSED EVALUATION
During the course of resuscitation, the clinician should obtain a focused history from a family
member or caregiver to determine:
● Prehospital administration of benzodiazepines and any antiseizure medications

● Patient history of epilepsy
● Precipitating factors prior to seizure (eg, acute illness, possible toxic exposure, trauma,
change in antiseizure medications)
● Current medications, including prior or current use of antiseizure medications
● For patients with prior status epilepticus, history of treatment response
● Other active medical diagnoses
In patients with status epilepticus, the initial physical examination is limited:

● A focused general medical evaluation should assess respiratory and circulatory status.
Attention to airway, breathing, and circulation is urgent, as in other medical emergencies.
The examiner should also look for signs of head trauma, sepsis, anisocoria or meningitis.
● A rapid neurologic examination should be performed to determine the type of status

epilepticus and, if possible, its etiology.
IMMEDIATE SUPPORTIVE CARE
Approach — In patients with convulsive status epilepticus, immediate supportive care must
occur simultaneously with prompt administration of antiseizure medications ( algorithm 1).
The main goals of care are:
● Establish and maintain adequate airway, breathing, and circulation

● Stop the seizure and thereby prevent brain injury
● Identify and treat life-threatening causes of status epilepticus, such as trauma, sepsis,
meningitis, encephalitis, or structural brain lesion
Monitoring — All patients with generalized convulsions should have continuous monitoring of

heart rate and rhythm, breathing, pulse oximetry, and periodic measurement of blood pressure
and temperature. However, continuous motor activity may interfere with the ability of electronic
monitors to detect abnormalities. Thus, frequent clinical assessment of breathing, pulse, and
color must supplement monitor readings to ensure rapid detection of apnea, cyanosis, or
shock.
Measurement of arterial blood gases is often valuable, as most patients with generalized
convulsive status epilepticus (GCSE) who do not respond rapidly to initial treatment require
intubation and mechanical ventilation. However, in general, one should use clinical findings
when deciding whether to perform endotracheal intubation rather than rely exclusively on
blood gas findings, as the combined metabolic and respiratory acidosis can result in
overestimation of respiratory compromise by blood gas monitoring. (See "The decision to
intubate".)
Airway and breathing — Important airway interventions in include:
● Maintaining an open airway through positioning maneuvers and airway devices as

needed. Some authors recommend against insertion of an oropharyngeal airway due in
part to the difficulty in placement, the associated risk of upper airway obstruction, and the
potential for injury to medical personnel placing the airway [2]. Nasopharyngeal airways
can be placed more easily and with less potential trauma to patient and medical
personnel. (See "Basic airway management in adults", section on 'Airway adjuncts'.)
● Administering 100 percent oxygen and assessing for cyanosis by visual appearance and
pulse oximetry.
For patients with transient apnea or hypoxemia, the clinician may use bag-mask ventilation as
long as the airway can be maintained and spontaneous breathing with adequate oxygenation
resumes within a short period of time. (See "Basic airway management in adults", section on
'Bag-mask ventilation'.)
Patients with any one of the following should undergo rapid sequence endotracheal intubation
(RSI) and mechanical ventilation:
● Unprotected or unmaintainable airway

● Apnea or inadequate ventilation
● Hypoxemia
● Status epilepticus lasting ≥30 minutes
● Need to protect airway for urgent brain imaging (eg, in a patient with preceding trauma or
signs of basilar territory stroke)
After administering an induction agent such as propofol or midazolam, neuromuscular blocking

agents may help to facilitate rapid successful RSI. Using an induction agent that has antiseizure
activity such as propofol (see "Refractory status epilepticus in adults", section on 'Propofol')
makes theoretical sense in this setting. Etomidate is not considered a first-line induction agent
because it has been associated with a slightly increased risk of seizure activity.
While neuromuscular blocking agents block the motor manifestations, they do not treat the
underlying seizure activity; therefore, electroencephalography (EEG) monitoring is mandatory in
order to know whether GCSE has resolved or is continuing and needs further treatment. Some
experts advise against depolarizing blocking agents such as succinylcholine due to the risk of
exacerbating hyperkalemia in patients with recent seizures or those found down with
prolonged immobilization. While succinylcholine (duration of action four to six minutes) is
shorter acting than rocuronium and vecuronium (duration of action 30 to 40 minutes), the latter
drugs can be easily reversed with sugammadex if necessary.
EEG monitoring is especially important when a second dose of a longer-acting paralytic is given
to facilitate diagnostic studies such as computed tomography (CT) scanning or lumbar
puncture. If longer-acting paralytics are used without EEG monitoring, it would not be clear if or
when the GCSE had stopped.
RSI and the use of induction agents and neuromuscular blocking agents are reviewed in detail
separately. (See "Rapid sequence intubation for adults outside the operating room" and
"Induction agents for rapid sequence intubation in adults outside the operating room", section
on 'Status epilepticus' and "Neuromuscular blocking agents (NMBAs) for rapid sequence
intubation in adults outside of the operating room".)
Circulation and vascular access
● Establish venous access – Patients with status epilepticus require timely vascular access
for sampling of blood and administration of medications and fluids. Peripheral
intravenous (IV) access with at least two catheters should be established as soon as
possible. Alternative routes of antiseizure medication administration (eg, rectal,
intramuscular [IM], buccal, or intranasal) should be used if IV administration is not
possible within the first five minutes; an intraosseous (IO) line should be placed if IV
access is further delayed. Many antiseizure medications can be given via the IO route if IV
access is not available, including all benzodiazepines, phenytoin, and levetiracetam [3].
However, IO administration in adults is not as well studied as IM or IV administration.
● Hemodynamic support – Status epilepticus does not independently cause hypotension,

at least early in its course; the presence of hypotension in patients presenting with status
epilepticus should prompt consideration of an underlying systemic condition, cardiogenic
cause, traumatic hemorrhage, or sepsis. In addition, the presence of oliguria, tachypnea,
poor perfusion (eg, cool, clammy skin), and metabolic acidosis are warning signs that
point to shock and tissue hypoxia.
Hypotension may also result from benzodiazepines, barbiturates, and sedative/anesthetic

agents used to treat status epilepticus.
Patients with suspected shock should receive hemodynamic support with IV fluids (usually
crystalloids in boluses of 500 to 1000 mL), followed by vasopressors ( table 1) if IV fluids
fail to restore adequate tissue perfusion.
Initial studies — Initial blood and urine studies should be obtained for rapid determination of:
● Serum glucose and a rapid "finger-stick" or point-of-care glucose

● Serum electrolytes
● Calcium, phosphorus, and magnesium
● Liver function tests
● Complete blood count
● Serum antiseizure medication levels, if applicable
● Urine and blood toxicology

● Qualitative pregnancy test (urine or blood) in women of childbearing age
Other studies may also be indicated based upon the most likely underlying cause. Serum
lactate is often checked, as elevated or increasing levels may suggest hypoperfusion or
underlying infection.
These tasks require at least one to five minutes and should overlap with the next phase of
treatment ( algorithm 1).
Correct hypoglycemia and metabolic derangements — Hypoglycemia should be treated with

100 mg of thiamine and 50 mL of 50 percent dextrose solution. If IV access is not available, IM
glucagon or IO 50 percent dextrose can be given.
Hypoglycemia may provoke seizures and convulsive status epilepticus. Although uncommon,
either severe hyponatremia or hypocalcemia may cause status epilepticus that is refractory to
antiseizure medication and requires timely correction. Metabolic acidosis is often present in
patients with status epilepticus and can be severe, but it usually resolves without treatment
once seizures are controlled.
Suspicion for isoniazid poisoning — Pyridoxine (vitamin B6) treatment is required for all
patients with seizures or GCSE from acute isoniazid (INH) poisoning. Clinicians should suspect
INH as a possible cause of seizures when the patient or a patient's family member is being
treated with INH or has emigrated from an area where tuberculosis infection is endemic or
when seizures fail to respond to appropriate benzodiazepine therapy. (See "Isoniazid (INH)
poisoning", section on 'Seizure management'.)
EMERGENCY ANTISEIZURE TREATMENT
Many possible pharmacologic approaches to status epilepticus have been developed

empirically, but there are few controlled trials comparing different regimens. The approach
outlined below is generally consistent with consensus-based guidelines published by the
Neurocritical Care Society and the American Epilepsy Society [4,5].
Generalized convulsive status epilepticus (GCSE) — Clinically obvious GCSE should be treated

immediately with a benzodiazepine and a long-acting antiseizure medication, without waiting
for an electroencephalogram (EEG) or other studies ( algorithm 1). Treatment delay is
associated with increased morbidity and mortality.

First therapy: Benzodiazepines — Benzodiazepines are the first-line treatment for convulsive

status epilepticus because they control seizures rapidly [6-11]. The three most commonly used
benzodiazepines for status epilepticus are diazepam, lorazepam, and midazolam. In adults,
choice of benzodiazepine medication varies by route of administration [7]:
● Lorazepam is preferred for intravenous (IV) administration

● Midazolam is preferred for intramuscular (IM), intranasal, or buccal administration
● Diazepam is preferred for rectal administration
In addition to benzodiazepines, treatment with an intravenous nonbenzodiazepine antiseizure

medication (eg, levetiracetam, fosphenytoin, or valproate preferred; or lacosamide or
phenobarbital as alternatives) is given to prevent recurrence, even if convulsions have ceased
following benzodiazepine treatment [4,5]. (See 'Second therapy: Antiseizure medications'
below.)
Prehospital treatment — Benzodiazepine treatment of status epilepticus out of hospital

appears to be safe and effective using the following medications [8,9,12-15].
● Midazolam 10 mg IM and lorazepam 4 mg IV and are the best-studied drugs in this

setting.
● Clonazepam 1 mg IV is an option in Europe and elsewhere but is not available in IV form in

the United States.
● Rectal diazepam is given in doses of 0.2 mg/kg up to 20 mg for an adult [15].
● Buccal and nasal midazolam are also promising for outpatient interruption of seizures or
status epilepticus and can be administered without IV access or medical personnel [12].
The typical dose of buccal midazolam is 0.2 mg/kg, or 10 mg in adolescents and adults.
Intranasal midazolam can be given as a metered spray of 0.1 mL containing 0.5 mg (a
solution of 5 mg/mL), three to five times per nostril, and repeated if necessary, to a total
dose of 10 mg for adults.
In-hospital treatment — Pharmacologic therapy begins with a benzodiazepine and a

nonbenzodiazepine antiseizure medication ( algorithm 1). Despite initial treatment,
approximately 20 percent of patients develop refractory status epilepticus and require
additional therapy [16]. (See "Refractory status epilepticus in adults".)
Inadequate dosing of benzodiazepine is a common problem leading to prolongation of status

epilepticus [17].

● When IV or intraosseous access is available – Lorazepam 0.1 mg/kg should be

administered intravenously at a maximum rate of 2 mg/minute, allowing a few minutes
(eg, three to five minutes) to assess its effect before deciding whether additional doses are
necessary [4]. An alternative to a weight-based initial loading dose of lorazepam is a 4 mg
fixed dose, repeated if still seizing.
If seizures continue at this point, additional doses of lorazepam can be infused at a

maximum rate of 2 mg/minute. There is no definite maximum cumulative dose of
lorazepam; clinicians must be guided by the clinical effect (including on blood pressure)
and seizure control, both clinically and by EEG, once available. Even if seizure activity stops
following lorazepam, a loading dose of a nonbenzodiazepine antiseizure medication
should follow in order to maintain seizure control.
Diazepam 0.15 mg/kg IV, up to 10 mg per dose, may be substituted if lorazepam is not
available.
● When IV/intraosseous access is not available – Placement of an access catheter may be

difficult in some patients. When IV or intraosseous (IO) access cannot be achieved within
the first three minutes, IM midazolam is a safe and effective alternative for initial
benzodiazepine therapy [8,18,19]. As nasal and buccal midazolam are absorbed more
rapidly than IM midazolam, it is possible or even likely that these routes are superior [20],
but they are not as well studied as IM midazolam in adults.
For patients with a body weight >40 kg, midazolam can be given at a dose of 10 mg by IM,
nasal, or buccal administration [8,12]. With buccal administration of midazolam, one
report suggests that a dose of 15 to 20 mg for adults may be effective (when necessary)
and well tolerated [21].
Benzodiazepine efficacy — In a randomized, double-blind study of 205 patients with

status epilepticus, status epilepticus was terminated by arrival at the emergency department in
more patients treated with IV lorazepam or diazepam than placebo (59, 43, and 21 percent,
respectively) [9]. Of note, either benzodiazepine treatment also reduced the rates of respiratory
or circulatory complications compared with placebo (10.6, 10.3, and 22.5 percent, respectively),
lessening concern for the respiratory side effects of benzodiazepines.
● Lorazepam – Use of lorazepam as a first-line agent is supported by the Veterans Affairs

(VA) comparative trial that randomly assigned 570 patients with a confirmed diagnosis of
status epilepticus to one of four initial regimens: lorazepam (0.1 mg/kg), phenytoin (18
mg/kg), diazepam (0.15 mg/kg) plus phenytoin (18 mg/kg), or phenobarbital (15 mg/kg)
[6]. Status epilepticus was diagnosed after 10 minutes of seizure activity, clinically or on
EEG. In the subgroup of 384 patients with "overt" (clinically evident) GCSE, treatment with
lorazepam alone was most effective in terminating seizures within 20 minutes and in
maintaining seizure freedom for the first 60 minutes after treatment (65 percent versus 58
percent with phenobarbital, 56 percent with diazepam plus phenytoin, and 44 percent
with phenytoin alone), although the only statistically significant difference was between
lorazepam alone and phenytoin alone.
No significant differences in the success rates of the different regimens were observed in
the 134 patients with "subtle" GCSE (ie, status epilepticus evident on EEG after convulsions
had ceased, with some residual myoclonic jerking or eye movements as the only clinical
signs of ongoing seizures), and overall there were no significant differences in seizure
recurrence during the 12-hour study period, outcome at 30 days, or in the incidence of
adverse events [6]. Success with any regimen was much lower for "subtle" GCSE compared
with "overt" GCSE. Almost half of the patients with "overt" GCSE required additional
treatment with a second antiseizure medication, but when the first medication failed, only
7 percent of patients responded successfully to a second antiseizure medication.
The purported clinical advantage of lorazepam over diazepam is that the effective
duration of action against seizures is as long as four to twelve hours because of its less
pronounced redistribution into adipose tissue. The time from its injection to its maximum
effect against seizures is as long as two minutes. Nevertheless, a randomized clinical trial
in children with status epilepticus found that lorazepam and diazepam were similarly
effective in terminating seizures, with no difference in the rate of assisted ventilation [22].
(See "Management of convulsive status epilepticus in children", section on
'Benzodiazepine efficacy and pharmacokinetics'.)
● Diazepam – Diazepam has high lipid solubility and can therefore cross the blood-brain
barrier rapidly. It is highly effective in terminating seizures rapidly when administered
intravenously at doses of 0.1 to 0.15 mg/kg, up to 10 mg per dose. An effect upon seizure
activity can be seen as early as 10 to 20 seconds after administration, and cerebrospinal
fluid concentrations reach half of their maximum value in three minutes. Because of
subsequent redistribution of the drug into adipose tissue, however, the duration of
diazepam's acute anticonvulsant effect is typically <20 minutes. Initial termination of
seizure activity with IV diazepam is seen in 50 to 80 percent of patients [6], but if no other
medication is provided, there is a 50 percent chance of seizure recurrence within the next
two hours [23,24].
Nonetheless, IV diazepam remains the drug of first choice in some settings because it is
stable in liquid form for long periods at room temperature. Thus, diazepam is available in
resuscitation kits in premixed form, while lorazepam [25] and phenytoin are not.
A rectal gel formulation of diazepam provides rapid delivery when IV access is difficult, or
for at-home use for patients who have frequent repetitive or prolonged seizures [26]. A
nasal spray formulation of diazepam is also available [27]; it is approved by the US Food
and Drug Administration (FDA) for the acute treatment of intermittent, stereotypic
episodes of frequent seizure activity (ie, seizure clusters, acute repetitive seizures) in
patients age six years and older [28].
● Midazolam – Like lorazepam and diazepam, midazolam is very effective in terminating

seizures rapidly (frequently in less than one minute), but it has a short half-life in the
central nervous system. Midazolam appears to be quite stable at ambient temperatures in
ambulances [25]. IM, nasal, and buccal administration of midazolam (0.2 mg/kg,
maximum 10 mg) are effective alternatives to IV lorazepam when IV access is difficult
[19,21,29,30]. In a randomized trial of 898 patients with status epilepticus in the
prehospital setting, 10 mg IM midazolam was superior to 4 mg IV lorazepam in adults [8].
On arrival to hospital, patients receiving IM midazolam had a higher rate of seizure control
(73 versus 63 percent) than patients receiving IV lorazepam. The superiority of IM
administration arose from the time required to insert an IV; the treatment response with
IV lorazepam was faster compared with IM midazolam (1.6 versus 3.3 minutes) if counted
from the time of medication administration, while time to treatment administration was
shorter with midazolam compared with lorazepam-treated patients (1.2 versus 4.8
minutes). Adverse reactions were similar for both treatments.
Continuous infusion of IV midazolam is used in the management of refractory status

epilepticus. (See "Refractory status epilepticus in adults", section on 'Midazolam'.)
● Clonazepam – Outside the United States, IV clonazepam (0.015 mg/kg) is commonly used
as a first-line therapy for status epilepticus [13,31]. Although comparative data are
relatively limited, one observational study found that first-line therapy with clonazepam
was associated with a lower risk for refractory status epilepticus compared with
lorazepam, even after adjusting for relevant confounders [17]. The study also raised
concern that lorazepam was given in inadequate doses more often than clonazepam,
perhaps explaining some of the difference in efficacy. A randomized trial in 107 adults with
status epilepticus found that prehospital administration of levetiracetam (2.5 grams IV)
plus clonazepam (1 mg IV, repeated at 5 minutes for ongoing seizures) offered no benefit
over clonazepam alone [13]. Rates of seizure cessation at 15 minutes were similar for
combined treatment compared with clonazepam alone (74 versus 84 percent, 95% CI for
percentage difference -24 to 3), as were all secondary endpoints, including rates of
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recurrent seizure activity, need for intubation, and length of hospital stay. Of note, IV
clonazepam is not available in the United States but is commonly used in Europe as a first-
line agent.
Second therapy: Antiseizure medications — As noted above, treatment with a

nonbenzodiazepine antiseizure medication is given to prevent recurrence, even if convulsions
have ceased following benzodiazepine treatment [4,5]. It is important to calculate the weight-
based dose; underdosing of antiseizure medication should be avoided.
Choosing an agent — We suggest treatment with either levetiracetam, fosphenytoin, or

valproate, rather than alternative antiseizure medications.
● Levetiracetam – Levetiracetam is given at a loading dose of 60 mg/kg (maximum 4500

mg) infused over 15 minutes. (See 'Levetiracetam' below.)
● Fosphenytoin and phenytoin – Fosphenytoin is started with a loading dose of 20 mg

phenytoin equivalents (PE)/kg infused at 100 to 150 mg PE/min; phenytoin is started with
a loading dose of 20 mg/kg and infused at 25 to 50 mg/minute. The infusion rate should
be reduced if significant adverse effects occur. An additional dose of fosphenytoin 5 to 10
mg PE/kg (or phenytoin 5 to 10 mg/kg) can be given 10 minutes after the loading infusion
if seizures persist, up to a maximum cumulative dose of 30 mg/kg.
Phenytoin (but not fosphenytoin) is incompatible with any of the benzodiazepines and will
precipitate if infused through the same IV line; the same applies to phenytoin and any
fluid with glucose/dextrose. (See 'Fosphenytoin and phenytoin' below.)
● Valproate – Valproate is given with a loading dose of 40 mg/kg and infused at a rate of 10
mg/kg per minute in adults (maximum dose 3000 mg).
Factors influencing choice — The choice among antiseizure medications can be made

according to individual patient factors such as comorbid conditions and potential adverse
effects, as well as local availability and clinician experience.
For patients already on chronic therapy with one of the preferred agents prior to the onset of
status epilepticus, clinical judgement is required to determine nonbenzodiazepine antiseizure
medication selection and dosing for GCSE. As examples:
● For a patient on phenytoin treatment prior to the onset of GCSE who is known to have a
recent therapeutic phenytoin dose or level, it is reasonable to use valproate or
levetiracetam (rather than phenytoin or fosphenytoin) as the second agent for GCSE.

● For a patient on chronic valproate who is known to have a recent therapeutic dose or level,
it is reasonable to use fosphenytoin/phenytoin or levetiracetam (rather than valproate) as
the second agent for GCSE.
● For a patient on chronic phenytoin or valproate who is thought to have a low drug level,
an additional, proportionate loading dose of that drug would be worthwhile.
● For a patient on chronic levetiracetam, it takes too long to obtain levetiracetam levels in
the urgent setting of GCSE. Accordingly, it is reasonable to use fosphenytoin/phenytoin or
valproate as the second agent for GCSE if the recent dosing or level of levetiracetam is
unknown. An alternative is to reload with levetiracetam, as there is no serious risk to
transient supratherapeutic levetiracetam levels.
Antiseizure medication efficacy
Comparative efficacy — Among the antiseizure medications that can be loaded

intravenously, there is high-quality evidence from the Established Status Epilepticus Treatment
Trial (ESETT) trial that fosphenytoin, valproate, and levetiracetam are equally effective and have
similar rates of adverse effects [32]. The trial enrolled 384 pediatric and adult patients with
convulsive status epilepticus refractory to benzodiazepines. The patients were randomly
assigned to receive levetiracetam (n = 145 patients), fosphenytoin (n = 118), or valproate (n =
121). The trial was stopped early when an interim analysis met criteria for futility. The
composite outcome of cessation of status epilepticus and improvement in the level of
consciousness at 60 minutes was achieved in the levetiracetam group by 47 percent (95%
credible interval 39-55), in the fosphenytoin group by 45 percent (95% credible interval 36-54),
and in the valproate group by 46 percent of patients (95% credible interval 38-55). Although not
statistically significant, there were numerically more episodes of hypotension and intubation in
the fosphenytoin group and more deaths in the levetiracetam group compared with the other
groups. Limitations to the ESETT include a substantial rate (approximately 50 percent) of
unblinding of investigators and clinicians to permit choosing a second antiseizure medication
for ongoing seizures; inadvertent enrollment of patients without status epilepticus, including
patients with psychogenic nonepileptic seizures (approximately 10 percent of the study
population); capping of weight-based dosing at 75 kg (such that heavier patients received a
lower mg/kg dose); and absence of confirmatory EEG.
Prior to the ESETT, there were few high-quality data to guide the choice among the antiseizure
medications for treating status epilepticus. The earlier evidence came from observational
studies and a few smaller randomized trials; most of these reports suggested that phenytoin,

valproate, and levetiracetam had similar efficacy for treating status epilepticus, but the findings
for phenytoin were inconsistent [33-35].
Levetiracetam — We start levetiracetam using a loading dose of 60 mg/kg IV in adults

(maximum 4500 mg) infused over 15 minutes [32]. Status epilepticus guidelines differ in the
ranges provided for a single dose of levetiracetam IV; one suggests 1000 to 3000 mg IV in
adults [4], and the other suggests 60 mg/kg up to a maximum of 4500 mg [5]. Doses are
typically infused over 15 minutes [36]. Retrospective data suggest that rapid intravenous
infusion of levetiracetam in doses up to 4500 mg is safe and well-tolerated [37].
Although high-quality evidence to guide individual patient therapy is lacking, levetiracetam may
be preferred for patients with status epilepticus who are already receiving levetiracetam at
baseline and for those with liver failure. Levetiracetam is increasingly commonly used in this
setting, in part for its lack of interactions with other drugs, an advantage when transitioning to
longer-term medication regimens.
Fosphenytoin and phenytoin
● Fosphenytoin – Fosphenytoin is the generally preferred formulation of phenytoin for

rapid intravenous dosing. The loading dose is 20 mg PE/kg, infused at a rate of 100 to 150
mg PE/minute. Cardiac monitoring and frequent vital signs are required during the
infusion of fosphenytoin or phenytoin and for at least 15 minutes after the end of a
fosphenytoin infusion while it continues to be dephosphorylated into phenytoin
(conversion half-life is 15 minutes).
Fosphenytoin is a pro-drug of phenytoin that is hydrolyzed to phenytoin by serum

phosphatases. It is highly water soluble and therefore unlikely to precipitate during IV
administration. The risk of local irritation at the site of infusion is significantly reduced
compared with phenytoin; fosphenytoin can therefore be infused much more rapidly (up
to 150 mg PE/minute versus 50 mg/minute with phenytoin). In addition, the increased
water solubility of fosphenytoin makes IM administration possible if IV access cannot be
obtained. IM administration, however, yields less predictable levels and a longer time to
onset of effect than IV administration and should not be used for convulsive GCSE.
Because propylene glycol is not required to solubilize fosphenytoin, the cardiovascular

side effects of fosphenytoin, especially hypotension, may be less frequent and severe than
those of phenytoin, but at least two studies have suggested that the incidence of adverse
hemodynamic effects with fosphenytoin and phenytoin infusions is similar [38,39].

Phenytoin and fosphenytoin are reported to intensify seizures caused by cocaine, other
local anesthetics, theophylline, or lindane [40-42].
● Phenytoin – Phenytoin is generally started with a loading dose of 20 mg/kg, infused at a

rate of up to 50 mg/minute. A common error is giving a "standard" dose of 1 gram, which
is inadequate dosing for most patients weighing more than 50 kg (110 pounds), ie, most
adults. It is critical to modify the infusion rate if hypotension or other adverse
cardiovascular events occur. The risks of hypotension and cardiac arrhythmias increase
with higher infusion rates, partly due to the propylene glycol used to solubilize phenytoin.
In addition, the risks of local pain and injury (including venous thrombosis and the rare
purple glove syndrome) increase with more rapid infusions. Cardiac monitoring during the
initial infusion is mandatory because cardiac arrhythmias may occur.
Valproate — Intravenous valproate is increasingly used in the treatment of status

epilepticus. It is preferred over phenytoin in patients with primary generalized epilepsies,
although these patients represent a relatively small proportion of those with GCSE. It can also
be particularly useful as a nonsedating option in patients with focal or myoclonic status
epilepticus (MSE).
Accumulating evidence suggests that a loading dose of 40 mg/kg can be infused safely at a rate
of 10 mg/kg per minute (maximum dose 3000 mg) in adults without adverse effects on blood
pressure or heart rate [5,32]. Loading doses in this range yield concentrations in typical
therapeutic ranges and without significant sedation. Patients who are already on enzyme-
inducing antiseizure medications may need higher doses, and the free phenytoin level may rise
with concurrent administration. (See "Antiseizure medications: Mechanism of action,
pharmacology, and adverse effects", section on 'Valproate'.)
The risk of hepatic toxicity and hyperammonemic encephalopathy due to valproate may pose
diagnostic challenges in postictal settings [43], particularly in children with some
aminoacidopathies. Risks of hepatic dysfunction and coagulopathy are important
considerations in patients with active bleeding. (See "Valproic acid poisoning".)
Second- or third-line medications — There are several antiseizure medications that

can be useful in the management of status epilepticus but are not preferred as initial drugs in
most cases due to adverse effect profile or lack of sufficient data on efficacy [4,5].
Phenobarbital and lacosamide can be given intravenously and may be particularly useful as
adjunctive agents in patients with focal or nonconvulsive status epilepticus, as an additional
treatment in patients with refractory status epilepticus, and (for lacosamide) when preservation
of a higher level of consciousness is desired.
● Phenobarbital – Phenobarbital is a very effective anticonvulsant, especially in the acute

management of seizures, but it was not the best initial treatment in the VA comparative
trial [6]. Various studies have shown a rate of seizure control of approximately 60 percent
when phenobarbital is used alone, similar to that with lorazepam alone or the
combination of phenytoin and diazepam [6,44]. High doses of phenobarbital will control
almost any seizure [45], but at the cost of substantial sedation and potential reduction of
blood pressure and respiration. Despite its efficacy, phenobarbital is generally not used as
a first-line treatment in adults because it is slow to administer, causes prolonged sedation,
and may involve a higher risk of hypoventilation and hypotension than benzodiazepines,
phenytoin, valproate, or levetiracetam.
Initial doses of phenobarbital 20 mg/kg infused at a rate of 30 to 50 mg/minute are

generally used; slower infusion rates should be used in older adult patients, although
phenobarbital may have fewer cardiac side effects than phenytoin in these patients.
Careful monitoring of respiratory and cardiac status is mandatory. Intubation is often
necessary in order to provide a secure airway and minimize the risk of aspiration if
phenobarbital is administered following benzodiazepines. The risk of prolonged sedation
with phenobarbital is greater than with the other antiseizure medications, in part because
of its half-life of 87 to 100 hours.
● Lacosamide – Accumulating data indicate that IV lacosamide (200 to 400 mg IV bolus) is

usually well tolerated and may have similar efficacy compared with other agents used to
treat refractory status epilepticus [46-54]; rare serious adverse events include second-
degree and complete atrioventricular block [46]. An electrocardiogram should be
performed before use of lacosamide and during maintenance to monitor for PR
prolongation. Additional caution is warranted in patients with comorbid heart disease and
with concurrent use of other drugs that may prolong the PR interval.
Refractory GCSE — Optimally, treatment of GCSE with benzodiazepines and antiseizure

medications is completed within 10 to 20 minutes ( algorithm 1). In patients with GCSE who
are actively seizing at 30 minutes despite two initial doses of a benzodiazepine and
administration of an antiseizure medication, preparation for a continuous infusion of
midazolam, propofol, or pentobarbital should begin. At this stage, the patient will require
endotracheal intubation and mechanical ventilation (if not already performed), neurologic
consultation, and transfer to an intensive care unit with continuous EEG (cEEG) monitoring
capability, as reviewed separately. (See "Refractory status epilepticus in adults".)
Focal motor status epilepticus — Most focal status epilepticus is treated with the same
antiseizure medications as for GCSE, but with somewhat less urgency and with higher priority
given to the avoidance of oversedation and intubation. (See 'Generalized convulsive status
epilepticus (GCSE)' above.)
● Nonketotic hyperglycemia – When focal motor status is caused by nonketotic

hyperglycemia, seizures are usually controlled readily with correction of the metabolic
derangements [55]. Benzodiazepines can be used if seizures persist despite correction.
Antiseizure medications are often unnecessary after resolution of the acute illness. (See
"Diabetic ketoacidosis and hyperosmolar hyperglycemic state in adults: Treatment".)
● Epilepsia partialis continua – For the more prolonged episodes of epilepsia partialis
continua, antiseizure medications including benzodiazepines may be helpful and
necessary in preventing secondarily generalized seizures, but they often do not stop the
continued focal jerking, even with multiple antiseizure medications. Overall, treatment is
seldom very effective. Surgical treatment can be pursued if the responsible lesion is clearly
identified and small enough, but it is not always successful [56].
Myoclonic status epilepticus — Initial treatment of MSE is heavily dependent upon the form of
MSE and the underlying etiology. (See "Convulsive status epilepticus in adults: Classification,
clinical features, and diagnosis", section on 'Myoclonic status epilepticus'.)
● Relatively benign MSE – MSE in the relatively benign epilepsy syndromes such as juvenile
myoclonic epilepsy (JME) is often recognized readily and treated relatively easily with
benzodiazepines; valproate and levetiracetam may also be helpful [57,58]. A primary
consideration in the treatment of these (presumed) genetic generalized epilepsies is the
avoidance of inappropriate use of sodium channel-based antiseizure medications such as
carbamazepine, phenytoin, and oxcarbazepine [59], which may exacerbate seizures.
Patients usually return to their baseline conditions relatively rapidly with treatment,
without residual morbidity. (See "Juvenile myoclonic epilepsy".)
● More severe MSE – The more severe forms of MSE that occur in (usually childhood-onset)
epilepsy syndromes, such as Lennox-Gastaut syndrome, can be much more difficult to
interrupt. Initial treatment is often with the antiseizure medications noted above but also
with those used for GCSE. Many of these MSE cases include nonconvulsive seizures
(sometimes difficult to distinguish from the baseline impaired cognition). Also, it can be
difficult to recognize when seizures have ceased, so cEEG monitoring is necessary in both
diagnosis and management. In the MSE associated with progressive myoclonic epilepsy
syndromes, treatment is similar to that for GCSE. Seizures may come under control, but
the underlying encephalopathy often progresses despite seizure cessation.

MSE due to medical illnesses causing encephalopathy (eg, uremia or sepsis) may be
refractory. The antiseizure medications used for convulsive status epilepticus may
interrupt the seizures, but the outcome depends primarily on treatment or management
of the underlying medical illness.
● Anoxic MSE – Anoxic MSE is completely different [60-62]. Benzodiazepines, valproic acid,
and levetiracetam can help control epileptiform discharges and clinical myoclonus, but the
underlying encephalopathy usually determines the outcome, which is very often poor,
although there are a few exceptions. (See "Hypoxic-ischemic brain injury in adults:
Evaluation and prognosis".)
POSTICTAL RECOVERY AND FURTHER EVALUATION
Expected pace of recovery — Most patients begin to recover responsiveness within 10 to 20

minutes after generalized convulsions, but there is a broad range. Close monitoring during this
period is important.
The two most common reasons for prolonged postictal recovery are sedation due to
medications and the continuation of (nonconvulsive) seizures; these can be impossible to
distinguish clinically. Note that benzodiazepine reversal with flumazenil should be avoided in
this setting, as reversal can precipitate seizures. Patients with seizures or status epilepticus who
do not return to a normal level of consciousness after initial treatment should be monitored by
electroencephalography (EEG) to determine if the patient is still seizing. (See 'EEG monitoring'
below.)
Neurologic assessment — During the postictal recovery period, it is important to repeat a full

neurologic examination, looking for asymmetric or focal findings that may suggest clues to the
underlying etiology.
EEG monitoring — For patients with status epilepticus as the first presentation of seizures or
epilepsy, an EEG should be done to evaluate background activity as soon as possible after the
seizure stops. An EEG may not be necessary for patients with known epilepsy who are
recovering as expected from status epilepticus if the clinicians are confident the clinical seizures
have stopped and there is no other independent reason that the patient would benefit from
ongoing continuous EEG (cEEG) monitoring.
All patients with seizures or status epilepticus who do not return to a normal level of
consciousness after initial treatment should be monitored by cEEG to determine whether
seizures have stopped. In a prospective study of 164 patients presenting with generalized
convulsive status epilepticus in which cEEG monitoring was performed postictally (beginning
within 30 minutes of control of clinical seizures), the following findings were described [63]:
● Fifty-two percent of patients had no evidence of ongoing epileptic discharges or seizures.

The most common EEG patterns in these patients were generalized slowing, background
voltage attenuation, lateralized periodic discharges (LPDs; previously known as periodic
lateralized epileptiform discharges [PLEDS]), focal slowing, or burst suppression. Mortality
in this subgroup was 13 percent.
● Fourteen percent of patients had evidence of nonconvulsive status epilepticus. All of these
patients were comatose and had no overt clinical signs of convulsive activity. The EEG
pattern was focal or focal with secondary generalization in most patients. Mortality in this
subgroup was 51 percent.
● In the remaining 34 percent of patients, EEG demonstrated evidence of noncontinuous

rhythmic discharges lasting 10 seconds to several minutes and considered to be
electrographic seizures, mostly without clinical accompaniment; mortality in this subgroup
was 32 percent.
Neuroimaging — For patients with status epilepticus as the first presentation of seizures or

epilepsy, those with suspected focal onset of status epilepticus, and/or patients who are not
recovering as expected, a head computed tomography (CT) or magnetic resonance imaging
(MRI) should be obtained once seizures are controlled. CT may be performed in the emergency
department setting, but MRI has superior yield for determining the underlying etiology. Some
experts obtain neuroimaging for everyone with status epilepticus. (See "Convulsive status
epilepticus in adults: Classification, clinical features, and diagnosis", section on 'Neuroimaging'.)
Lumbar puncture — A lumbar puncture (LP) for cerebrospinal fluid analysis is warranted if the
clinical presentation is suggestive of an acute infection that involves the central nervous
system, or if the patient has a history of a malignancy and there is concern for leptomeningeal
metastases. In other circumstances, LP is less likely to be helpful and may even be misleading,
because a prolonged seizure itself can cause cerebrospinal fluid pleocytosis (although usually
only minor). LP should only be performed after a space-occupying brain lesion has been
excluded by appropriate brain imaging studies; blood cultures should be obtained and empiric
antimicrobials should be started prior to brain imaging if there is concern for infection.
SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions
around the world are provided separately. (See "Society guideline links: Seizures and epilepsy in
adults".)
SUMMARY AND RECOMMENDATIONS
● Recognition and evaluation – Generalized convulsive status epilepticus (GCSE) is an

unremitting generalized convulsive seizure lasting longer than five minutes or frequent
motor seizures without an interictal return to the baseline level of consciousness. (See
'Rapid recognition of status epilepticus' above and 'Urgent focused evaluation' above.)
● Immediate supportive care – The initial assessment and treatment of a patient in status
epilepticus should proceed in quick succession and include ( algorithm 1):
• A focused history from a family member or caregiver, assessment of respiratory and

circulatory status, and a rapid neurologic examination. (See 'Urgent focused evaluation'
above.)
• Maintenance of an adequate airway, breathing, and circulation, and placement of

cardiorespiratory monitoring. (See 'Airway and breathing' above and 'Monitoring'
above.)
• Placement of two intravenous (IV) or intraosseous (IO) catheters and hemodynamic

support as required. (See 'Circulation and vascular access' above.)
• Laboratory studies including serum glucose (rapid point-of-care), electrolytes, calcium,

and magnesium; serum antiseizure medication levels (if applicable); and urine and
blood toxicology. (See 'Initial studies' above.)
• Correction of hypoglycemia and metabolic abnormalities. (See 'Correct hypoglycemia

and metabolic derangements' above.)
● Antiseizure treatment of GCSE – The pharmacologic management of GCSE is

summarized in the algorithm ( algorithm 1).
• Benzodiazepine – For patients presenting with GCSE, we recommend initial treatment

with a benzodiazepine (Grade 1A). When IV or IO access is readily available, lorazepam
is preferred over other benzodiazepines based on pharmacokinetic properties (Grade
2C). The typical loading dose of lorazepam is 0.1 mg/kg IV, infused at a maximum rate
of 2 mg/min, allowing three to five minutes to assess the effect before deciding
whether additional doses are necessary. An alternative is a fixed dose of lorazepam (4

mg), repeated if the patient is still seizing. (See 'First therapy: Benzodiazepines' above.)
In the prehospital setting, or if IV or IO access is delayed, intramuscular (IM)

midazolam (10 mg) is an effective alternative to IV lorazepam. Nasal or buccal
midazolam (0.2 mg/kg, maximum 10 mg) is also a reasonable option.
• Antiseizure medication – For patients presenting with GCSE, in addition to

benzodiazepines, ( algorithm 1) we suggest treatment with an IV loading dose of a
longer-acting antiseizure medication in order to maintain seizure control (Grade 2C).
Levetiracetam (60 mg/kg, maximum 4500 mg), fosphenytoin (20 mg phenytoin
equivalents [PE]/kg), or valproate (40 mg/kg) are all effective antiseizure medications in
this setting. (See 'Second therapy: Antiseizure medications' above.)
• Refractory GCSE – For patients with GCSE who are actively seizing at 30 minutes
despite treatment with benzodiazepines and antiseizure medication, preparation for a
continuous infusion of midazolam, propofol, or pentobarbital should begin. At this
stage, the patient will require endotracheal intubation and mechanical ventilation,
neurologic consultation, and transfer to an intensive care unit with continuous
electroencephalography (cEEG) monitoring capability. (See "Refractory status
epilepticus in adults".)
● Postictal recovery and assessment – The most common reasons for prolonged postictal
recovery are sedation due to medications and the continuation of (nonconvulsive)
seizures; these can be impossible to distinguish clinically. Patients who do not recover
responsiveness within 10 to 20 minutes after generalized convulsions require further
evaluation with cEEG. (See 'Postictal recovery and further evaluation' above.)
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Topic 96933 Version 56.0

GRAPHICS
Approach to the treatment of convulsive status epilepticus in adults


This algorithm summarizes our suggested approach to antiseizure treatment for convulsive status epilepticus
minutes or frequent clinical seizures without an interictal return to the baseline clinical state. Along with imme
initiation of monitoring, including supportive care of airway, breathing, and circulation, and rapid recognition a
nervous system infection, sepsis, and traumatic brain injury. The goal of therapy is to achieve seizure freedom
EEG). Refer to UpToDate topics on adult CSE for additional details.
EMS: emergency medical services; IV: intravenous; IO: intraosseous; LFT: liver function test; CBC: complete blo
IM: intramuscular; EEG: electroencephalogram; SE: status epilepticus; ICU: intensive care unit; RSI: rapid seque
nonconvulsive status epilepticus; CSE: convulsive status epilepticus; PE: phenytoin equivalents; LP: lumbar pun
* Rapid sequence intubation should be performed if airway, ventilation, or oxygenation cannot be maintained
¶ Refer to UpToDate topics on SE in adults for a complete list of ancillary studies.
Δ Common causes of CSE are listed here. For further discussion of causes of CSE in adults, refer to UpToDate to
◊ Usually the ASM used for initial or second therapy, unless an alternative ASM can be tailored to clinical circu
§ Additional evaluation may include neuroimaging if CSE is the first presentation of epilepsy or if there are new
concern for increased ICP, or prolonged duration of depressed consciousness (ie, for >1 to 2 hours after the ep
and empiric antimicrobials should be started prior to brain imaging, and LP should be performed after a space
details regarding the diagnostic evaluation in patients with CSE, refer to UpToDate topics on adult CSE.
¥ There is no definite maximum cumulative dose of lorazepam; clinicians should be guided by the clinical effec
‡ Phenytoin and fosphenytoin may be less effective for the treatment of seizures due to toxins or drugs and m
theophylline, or lindane. In such cases, levetiracetam, valproate, or phenobarbital should be used. Other clinic
an antiseizure medication); refer to UpToDate topics on adult CSE.
† If fosphenytoin is not available, IV phenytoin may be used (20 mg/kg IV; do not exceed 1 mg/kg per minute;
require cardiac monitoring.
Graphic 74649 Version 17.0

Vasopressors and inotropes in treatment of acute hypotensive states and

shock: Adult dose and selected characteristics
United Range of
Usual R
States maximum doses
Agent Initial dose maintenance
trade used in
dose range
name refractory shock
Vasopressors (alpha-1 adrenergic)
Norepinephrine Levophed 5 to 15 mcg/minute 2 to 80 mcg/minute 80 to

(noradrenaline) (0.05 to (0.025 to 250 mcg/minute (1
0.15 mcg/kg/minute) 1 mcg/kg/minute) to
3.3 mcg/kg/minute)
Cardiogenic shock: Cardiogenic shock:
0.05 mcg/kg/minute 0.05 to
0.4 mcg/kg/minute
Epinephrine Adrenalin 1 to 15 mcg/minute 1 to 40 mcg/minute 40 to

(adrenaline) (0.01 to (0.01 to 160 mcg/minute
0.2 mcg/kg/minute) 0.5 mcg/kg/minute) (0.5 to
2 mcg/kg/minute)

Phenylephrine Neo- 40 to 20 to 80 to
Synephrine, 160 mcg/minute 400 mcg/minute 730 mcg/minute
Vazculep until stabilized (0.25 to (1.1 to
(alternatively, 0.5 to 5 mcg/kg/minute) 9.1 mcg/kg/minute)
2 mcg/kg/minute)

Dopamine Inotropin 2 to 2 to 20 mcg/kg/minute

5 mcg/kg/minute 20 mcg/kg/minute

Antidiuretic hormone
Vasopressin Pitressin, 0.03 units/minute 0.01 to Doses

(arginine- Vasostrict 0.04 units/minute >0.04 units/minute
vasopressin) (not titrated) can cause cardiac
ischemia and
should be reserved
for salvage therapy
Inotrope (beta1 adrenergic)
Dobutamine Dobutrex Usual: 2 to 2 to 20 mcg/kg/minute

5 mcg/kg/minute 10 mcg/kg/minute
(range: 0.5 to
5 mcg/kg/minute;
lower doses for less
severe cardiac
decompensation)

Inotrope (nonadrenergic, PDE3 inhibitor)
Milrinone Primacor 0.125 to 0.125 to 0.75 mcg/kg/minute

0.25 mcg/kg/minute 0.75 mcg/kg/minute

All doses shown are for intravenous (IV) administration in adult patients. The initial doses shown in
this table may differ from those recommended in immediate post-cardiac arrest management (ie,
advanced cardiac life support). For details, refer to the UpToDate topic review of post-cardiac arrest
management in adults, section on hemodynamic considerations.
Vasopressors can cause life-threatening hypotension and hypertension, dysrhythmias, and
myocardial ischemia. They should be administered by use of an infusion pump adjusted by clinicians
trained and experienced in dose titration of intravenous vasopressors using continuous noninvasive
electronic monitoring of blood pressure, heart rate, rhythm, and function. Hypovolemia should be
corrected prior to the institution of vasopressor therapy. Reduce infusion rate gradually; avoid sudden
discontinuation.
Vasopressors can cause severe local tissue ischemia; central line administration is preferred. When a
patient does not have a central venous catheter, vasopressors can be temporarily administered in a
low concentration through an appropriately positioned peripheral venous catheter (ie, in a large vein)
for less than 24 hours. The examples of concentrations shown in this table are useful for peripheral
(short-term) or central line administration. Closely monitor catheter site throughout infusion to avoid
extravasation injury. In event of extravasation, prompt local infiltration of an antidote (eg,
phentolamine) may be useful for limiting tissue ischemia. Stop infusion and refer to extravasation
management protocol.
Vasopressor infusions are high-risk medications requiring caution to prevent a medication error and
patient harm. To reduce the risk of making a medication error, we suggest that centers have available
protocols that include steps on how to prepare and administer vasopressor infusions using a limited
number of standardized concentrations. Examples of concentrations and other detail are based on
recommendations used at experienced centers; protocols can vary by institution.
D5W: 5% dextrose water; MAP: mean arterial pressure; NS: 0.9% saline.
Prepared with data from:

1. Rhodes A, Evans LE, Alhazzani W, et al. Surviving sepsis campaign: International guidelines for management of sepsis and
septic shock: 2016. Crit Care Med 2017; 45:486.
2. Hollenberg SM. Vasoactive drugs in circulatory shock. Am J Respir Crit Care Med 2011; 183:847.
3. Lexicomp Online. Copyright © 1978-2021 Lexicomp, Inc. All Rights Reserved.

Graphic 99963 Version 19.0

Contributor Disclosures
Frank W Drislane, MD No relevant financial relationship(s) with ineligible companies to disclose. Paul
Garcia, MD Equity Ownership/Stock Options: EnlitenAI Inc [Epilepsy]. Consultant/Advisory Boards: Biogen
[Epilepsy]; Otsuka [Epilepsy]; Moon Creative Lab [Epilepsy]; EnlitenAI Inc [Epilepsy]. All of the relevant
financial relationships listed have been mitigated. Jonathan A Edlow, MD, FACEP No relevant financial
relationship(s) with ineligible companies to disclose. Alejandro A Rabinstein, MD Other Financial Interest:
Boston Scientific [Adverse event adjudication committee member for stroke risk reduction device in
patients with atrial fibrillation]; Boehringer Ingelheim [Adverse event adjudication committee member for
heart failure trial]. All of the relevant financial relationships listed have been mitigated. John F Dashe, MD,
PhD No relevant financial relationship(s) with ineligible companies to disclose.
Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are
addressed by vetting through a multi-level review process, and through requirements for references to be
provided to support the content. Appropriately referenced content is required of all authors and must
conform to UpToDate standards of evidence.
Conflict of interest policy

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24/12/21 13:01 Convulsive status epilepticus in adults: Management - UpToDate

Official reprint from UpToDate®

Convulsive status epilepticus in adults: Management

RAPID RECOGNITION OF STATUS EPILEPTICUS

https://www-uptodate-com.uandes.idm.oclc.org/contents/convulsive-status-epilepticus-in-adults-management/print?search=estatus epileptico&source… 1/36

require immediate assessment and treatment in an acute care setting (emergency

● Differential diagnosis – Few other conditions appear similar to generalized convulsive

• Psychogenic status epilepticus

The differential diagnosis of convulsive status epilepticus is reviewed in greater detail

Initial management involves rapid assessment and supportive treatment; urgent

URGENT FOCUSED EVALUATION

● Prehospital administration of benzodiazepines and any antiseizure medications

In patients with status epilepticus, the initial physical examination is limited:

https://www-uptodate-com.uandes.idm.oclc.org/contents/convulsive-status-epilepticus-in-adults-management/print?search=estatus epileptico&source… 2/36

● A rapid neurologic examination should be performed to determine the type of status

IMMEDIATE SUPPORTIVE CARE

The main goals of care are:

● Establish and maintain adequate airway, breathing, and circulation

Monitoring — All patients with generalized convulsions should have continuous monitoring of

Airway and breathing — Important airway interventions in include:

● Maintaining an open airway through positioning maneuvers and airway devices as

● Unprotected or unmaintainable airway

After administering an induction agent such as propofol or midazolam, neuromuscular blocking

Circulation and vascular access

● Hemodynamic support – Status epilepticus does not independently cause hypotension,

Hypotension may also result from benzodiazepines, barbiturates, and sedative/anesthetic

● Serum glucose and a rapid "finger-stick" or point-of-care glucose

● Urine and blood toxicology

Correct hypoglycemia and metabolic derangements — Hypoglycemia should be treated with

EMERGENCY ANTISEIZURE TREATMENT

Many possible pharmacologic approaches to status epilepticus have been developed

Generalized convulsive status epilepticus (GCSE) — Clinically obvious GCSE should be treated

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First therapy: Benzodiazepines — Benzodiazepines are the first-line treatment for convulsive

● Lorazepam is preferred for intravenous (IV) administration

In addition to benzodiazepines, treatment with an intravenous nonbenzodiazepine antiseizure

Prehospital treatment — Benzodiazepine treatment of status epilepticus out of hospital

● Midazolam 10 mg IM and lorazepam 4 mg IV and are the best-studied drugs in this

● Clonazepam 1 mg IV is an option in Europe and elsewhere but is not available in IV form in

● Rectal diazepam is given in doses of 0.2 mg/kg up to 20 mg for an adult [15].

In-hospital treatment — Pharmacologic therapy begins with a benzodiazepine and a

Inadequate dosing of benzodiazepine is a common problem leading to prolongation of status

https://www-uptodate-com.uandes.idm.oclc.org/contents/convulsive-status-epilepticus-in-adults-management/print?search=estatus epileptico&source… 7/36

● When IV or intraosseous access is available – Lorazepam 0.1 mg/kg should be

If seizures continue at this point, additional doses of lorazepam can be infused at a

● When IV/intraosseous access is not available – Placement of an access catheter may be

Benzodiazepine efficacy — In a randomized, double-blind study of 205 patients with

● Lorazepam – Use of lorazepam as a first-line agent is supported by the Veterans Affairs

● Midazolam – Like lorazepam and diazepam, midazolam is very effective in terminating

Continuous infusion of IV midazolam is used in the management of refractory status

Second therapy: Antiseizure medications — As noted above, treatment with a

Choosing an agent — We suggest treatment with either levetiracetam, fosphenytoin, or

● Levetiracetam – Levetiracetam is given at a loading dose of 60 mg/kg (maximum 4500

● Fosphenytoin and phenytoin – Fosphenytoin is started with a loading dose of 20 mg

Factors influencing choice — The choice among antiseizure medications can be made

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Antiseizure medication efficacy

Comparative efficacy — Among the antiseizure medications that can be loaded