Status Epilepticus

1. Presented by: Dave Jay S. Manriquez RN.
Status epilepticus (SE) refers to a life-threatening condition in which the brain is in a state of persistent
seizure. Definitions vary, but traditionally it is defined as one continuous unremitting seizure lasting
longer than 30 minutes (Annals of Emerg Med 2004; 43(5): 605-625), or recurrent seizures without
regaining consciousness between seizures for greater than 30 minutes. There is some evidence that 5
minutes is sufficient to damage neurons and that seizures are unlikely to self-terminate by that time. First
aid guidelines for seizures state that an ambulance should be called for seizures lasting longer than 5
minutes
This condition is most common in known epileptics. Within known epileptics, it can be caused by:
Insufficient dosage of a medication already prescribed to the patient. Such causes of this include:
•
• Forgetfulness on the part of the patient in taking scheduled doses, or failure to take doses
at the scheduled times
Dislike of the medication or its side effects
•
Patient's rationing of the medication. This is usually due to patient's difficulty in affording
•
medication, or temporary or permanent lack of access.
Failure to maintain a therapeutic level following a change in a patient's physiological needs. This
•
may be the result of a patient growing (into adolescence or adulthood), gaining weight,
pregnancy, or childbirth.
Sudden withdrawal from a seizure medication. Such causes include:
•
• Sudden lack of access to medication due to unexpected circumstances
Lack of ability for patient to communicate medication needs to others, leading to absence of doses
•
Physician's decision to discontinue medication
•
Consumption of alcoholic beverages while on an anticonvulsant, or alcohol withdrawal. For this
•
among other reasons, most patients who have active seizure disorders or who are on
anticonvulsants are advised to altogether avoid consuming alcohol.
Dieting or fasting while on an anticonvulsant. Those with epilepsy or who are on anticonvulsants
•
are advised to consult with their physicians prior to dieting or fasting.
Consuming certain food products that interact badly with an anticonvulsant (rare)
•
Starting on a new medication that reduces the effectiveness of the anticonvulsant
•
Developing a resistance to an anticonvulsant already being used
•
Injury to the patient. This may be the result of a sports injury, motor vehicle accident, fall,
•
physical abuse, or other injury that affects the brain. Though such injuries may trigger a seizure in
anyone, those with a known seizure disorder are more susceptible.
Developing a new, unrelated condition in which seizures are coincidentally also a symptom, but
•
are not controlled by an anticonvulsant already used
Metabolic disturbances
•
This condition may also occur as the first known seizure in new epileptics, accounting for about 10% of
cases. In non-epileptics, causes may include:
Brain disorders, such as:
•
• Meningitis
Encephalitis
•
Brain tumors
•
Abscess
•
Traumatic brain injury
•
Sepsis
•

2. Some autoimmune disorders
•
Extremely high fever, especially in children
•
Low glucose levels
•
Eating disorders
•
Nerve agents such as soman
•
Status epilepticus can be divided into two categories—convulsive and nonconvulsive, the latter of which
is underdiagnosed[citation needed].
Convulsive
Epilepsia partialis continua is a variant involving hour, day, or even week-long jerking. It is a
consequence of vascular disease, tumours, or encephalitis, and is drug-resistant.
Generalized myoclonus is commonly seen in comatose patients following CPR and is seen by some as an
indication of catastrophic damage to the neocortex.[4]
Nonconvulsive
Complex partial status epilepticus, or CPSE, and absence status epilepticus are rare forms of the
condition which are marked by nonconvulsive seizures. In the case of CPSE, the seizure is confined to a
small area of the brain, normally the temporal lobe. But the latter, absence status epilepticus, is marked
by a generalised seizure affecting the whole brain, and an EEG is needed to differentiate between the two
conditions. This results in episodes characterized by a long-lasting stupor, staring and unresponsiveness.
[edit] Benzodiazepines
Shortly after it was introduced in 1963, diazepam became the first choice for SE. Even though other
benzodiazepines such as clonazepam were useful, diazepam was relied upon almost exclusively. This
began to change in 1975 with a preliminary study on lorazepam conducted by Waltregny and Dargent,
who found that its pharmacological effects were longer lasting than those of an equal dose of diazepam.
[5] This meant it did not have to be repeatedly injected like diazepam,[6] the effects of which would wear
off 5–15 minutes later in spite of its 30-hour half-life (due to extensive redistribution of diazepam outside
the vascular compartment as diazepam is highly lipid soluble). It has also been found that patients who
were first tried on diazepam were much more likely to require endotracheal tubing than patients who
were first tried on phenobarbital, phenytoin,[7] or lorazepam.[8]
Today, the benzodiazepine of choice is lorazepam for initial treatment due to its long (2–8 hour) duration
of action and rapid onset of action, thought to be due to its high affinity for GABA receptors and to its
low lipid solubility which causes it to remain in the vascular compartment. If lorazepam is not available,
then diazepam should be given.[9] Sometimes, the failure of lorazepam alone is considered to be enough
to classify a case of SE as refractory.

3. [edit] Phenytoin and fosphenytoin
Phenytoin was once another first-line therapy, although the prodrug fosphenytoin can be administered
three times as fast and with far fewer injection site reactions. If these or any other hydantoin derivatives
are used, then cardiac monitoring is a must if they are administered intravenously. Because the
hydantoins take 15–30 minutes to work, a benzodiazepine or barbiturate is often co-administered.
Because of diazepam's short duration of action, they were often administered together anyway.
[edit] Barbiturates
Before the benzodiazepines were invented, there were the barbiturates, which are still used today if
benzodiazepines or the hydantoins are not an option. These are used to induce a barbituric coma. The
barbiturate most commonly used for this is phenobarbital. Thiopental or pentobarbital may also be used
for that purpose if the seizures have to be stopped immediately or if the patient has already been
compromised by the underlying illness or toxic/metabolic-induced seizures; however, in those situations,
thiopental is the agent of choice.
The failure of phenobarbital therapy does not preclude the success of a lengthy comatose state induced by
a stronger barbiturate such as secobarbital. Such was the case for Ohori, Fujioka, and Ohta ca. 1998,
when they induced a 10-month long coma (or quot;anesthesiaquot; as they called it) in a 26-year-old woman
suffering from refractory status epilepticus secondary to viral encephalitis and then tapered her off the
secobarbital very slowly while using zonisamide at the same time.[10]
[edit] General anesthetics
If this proves ineffective or if barbiturates cannot be used for some reason, then a general anesthetic such
as propofol[11] is tried; sometimes it is used second after the failure of lorazepam.[12] This also means
putting the patient on artificial respiration. Propofol has been shown to be effective in suppressing the
jerks seen in myoclonus status epilepticus, but as of 2002[update], there have been no cases of anyone
going into myoclonus status epilepticus, undergoing propofol treatment, and then not dying anyway.[13]
[edit] Lidocaine
The use of lidocaine in status epilepticus was first reported in 1955 by Bernhard, Boem and Hojeberg.
[14] Since then, it has been used in cases refractory to phenobarbital, diazepam, and phenytoin, and has
been studied as an alternative to barbiturates and general anesthetics.[15][16] Lidocaine is a sodium
channel blocker and has been used where sodium channel dysfunction was suspected.[17] However, in
some studies, it was either ineffective or even harmful for most patients.[18] The last is not so surprising
in light of the fact that lidocaine has been known to cause seizures in humans and laboratory animals at
doses greater than 15 µg/mL[19] or 2–3 mg/kg.

5. What is it?
Status epilepticus is a serious seizure disorder in which seizures do not stop. A seizure is a sudden
disruption of the brain's normal electrical activity, which can cause a loss of consciousness and make the
body twitch and jerk. This condition is a medical emergency.
Who gets it?
Status epilepticus can occur in anyone with epilepsy. It occurs more often in children who have an
underlying neurologic disorder or disease.
What causes it?
Status epilepticus is most often caused by not taking anticonvulsant medication as prescribed. It can also
be caused by an underlying condition, such as meningitis, sepsis, encephalitis, brain tumor, head trauma,
extremely high fever, low glucose levels, or exposure to toxins.
What are the symptoms?
The characteristic symptom of status epilepticus is seizures occurring so frequently that they appear to
be one continuous seizure. These seizures include severe muscle contractions and difficulty breathing.
Permanent damage can occur to the brain and heart if treatment is not immediate.
How is it diagnosed?
Status epilepticus is diagnosed according to its characteristic symptoms. The doctor will order tests to
look for the cause of the seizures. These may include blood tests, an electrocardiogram to check for an
abnormal heart rhythm; an electroencephalogram (EEG) to check electrical activity in the brain, and
magnetic resonance imaging (MRI) or computed tomography (CT) scans to check for brain tumors or
signs of damage to the brain tissue.
What is the treatment?
A person having a seizure should never be restrained. A child with status epilepticus should be taken to
the hospital immediately. There, medical personnel will stabilize the child with intravenous (IV)
anticonvulsant drugs and fluids. Other medications may be given intravenously to stabilize the child
until the seizures stop. The child may need a tube inserted through his or her nose or throat to maintain a
good airway for breathing, and he or she may also need to receive oxygen. General anesthesia may be
needed if status epilepticus resists treatment. The outlook for recovery in children is better than in
adults.
Self-care tips
If your child has been diagnosed with epilepsy, make sure he or she takes the medication as prescribed

6. Status epilepticus is an increasingly recognized public health problem in the A PDF version of this
United States. Status epilepticus is associated with a high mortality rate that document is available.
is largely contingent on the duration of the condition before initial treatment, Download PDF now (8
the etiology of the condition, and the age of the patient. Treatment is pages / 87 KB). More
evolving as new medications become available. Three new preparations-- information on using
fosphenytoin, rectal diazepam, and parenteral valproate--have implications PDF files.
for the management of status epilepticus. However, randomized controlled
trials show that benzodiazepines (in particular, diazepam and lorazepam)
should be the initial drug therapy in patients with status epilepticus. Despite
the paucity of clinical trials comparing medication regimens for acute
seizures, there is broad consensus that immediate diagnosis and treatment are
necessary to reduce the morbidity and mortality of this condition. Moreover,
investigators have reported that status epilepticus often is not considered in
patients with altered consciousness in the intensive care setting. In patients
with persistent alteration of consciousness for which there is no clear
etiology, physicians should be more quickly prepared to obtain
electroencephalography to identify status epilepticus. Physicians should rely
on a standardized protocol for management of status epilepticus to improve
care for this neurologic emergency. (Am Fam Physician 2003;68:469-76.
Copyright© 2003 American Academy of Family Physicians.)
Status epilepticus is an under-recognized health problem associated with substantial morbidity and
mortality. An estimated 152,000 cases occur per year in the United States, resulting in 42,000 deaths and
an inpatient cost of $3.8 to $7 billion per year.1-3 This review concentrates on the clinical management of
status epilepticus (particularly convulsive status epilepticus), the theoretic and clinical considerations
involved in choosing an antiepileptic drug to treat this emergency situation, and the consensus protocol
devised by the Epilepsy Foundation of America (EFA) Working Group on Status Epilepticus.
Definition, Classification, and Epidemiology
See page 406
DEFINITION
for definitions
A decade ago, the EFA convened a working group to define status epilepticus.4 They of strength-of-
described this condition as two or more sequential seizures without full recovery of evidence
consciousness between seizures, or more than 30 minutes of continuous seizure levels.
activity.4 This definition is generally accepted, although some investigators consider
shorter durations of seizure activity to constitute status epilepticus. Practically speaking, any person who
exhibits persistent seizure activity or who does not regain consciousness for five minutes or more after a
witnessed seizure should be considered to have status epilepticus.
CLASSIFICATION SCHEME
Status epilepticus is defined as two or more
Although there is no consensus over a classification
sequential seizures without full recovery of
system for status epilepticus, classification is necessary
consciousness between seizures, or more than
for appropriate management of the condition because
30 minutes of continuous seizure activity.
effective management depends on the type of status
epilepticus. In general, the various systems characterize
status epilepticus according to where the seizures arise--from a localized region of the cortex (partial
onset) or from both hemispheres of the brain (generalized onset). The other major categorization hinges

7. on the clinical observation of overt convulsions; thus,
status epilepticus may be convulsive or nonconvulsive
TABLE 1
in nature.
Systemic Complications of Generalized
Various approaches to classifying status epilepticus
Convulsive Status Epilepticus
have been suggested.5-7 One version5 classified status
epilepticus into generalized (tonic-clonic, myoclonic,
absence, atonic, akinetic) and partial (simple or
complex) status epilepticus. Another version6 divides Metabolic Renal
the condition into generalized status epilepticus (overt Lactic acidosis Acute renal failure
or subtle) and nonconvulsive status epilepticus (simple Hypercapnia from
partial, complex partial, absence). The third version7 Hypoglycemia rhabdomyolysis*
Hyperkalemia Myoglobinuria*
takes a different approach, classifying status epilepticus
Hyponatremia
by life stage (confined to the neonatal period, infancy
CSF/serum Cardiac/respirato
and childhood, childhood and adulthood, adulthood
leukocytosis ry
only).
Hypoxia
EPIDEMIOLOGY
Autonomic Arrhythmia
Status epilepticus of partial onset accounts for the Hyperpyrexia High output
majority of episodes.1-4,8-12 One epidemiologic study1 Failure of cerebral failure*
autoregulation* Pneumonia
on status epilepticus found that 69 percent of episodes
Vomiting
in adults and 64 percent of episodes in children were
Incontinence
partial onset, followed by secondarily generalized status
epilepticus in 43 percent of adults and 36 percent of
children. The incidence of status epilepticus was
bimodally distributed, occurring most frequently during
CSF = cerebrospinal fluid.
the first year of life and after the age of 60 years.1,2
*--Rare complications of status
Among adults, patients older than 60 had the highest
epilepticus.
risk of developing status epilepticus, with an incidence
Information from references 7 and 17
of 86 per 100,000 persons per year.1-3 Among children
through 19.
15 years or younger, infants younger than 12 months
had the highest incidence and frequency of status
epilepticus.1 A variety of etiologies accounted for the
condition. In adults, the major causes were low levels of antiepileptic drugs (34 percent) and
cerebrovascular disease (22 percent), including acute or remote stroke and hemorrhage.1-3
The rate of mortality from status epilepticus (defined as death within 30 days of status epilepticus) was
22 percent in the Richmond study.1,13 The mortality rate among children was only 3 percent, whereas the
rate among adults was 26 percent.1,13,14 The elderly population had the highest rate of mortality at 38
percent.1,13,14 The primary determinants of mortality in persons with status epilepticus were duration of
seizures, age at onset, and etiology.13,14 Patients with anoxia and stroke had a very high mortality rate
that was independent of other variables.13-15 Patients with status epilepticus occurring in the setting of
alcohol withdrawal or low levels of antiepileptic drugs had a relatively low mortality rate. In nonfatal
cases, status epilepticus is associated with significant morbidity. Cognitive decline following an episode,
as documented by neuropsychometric testing, is a well-established end result of prolonged secondarily
generalized and partial status epilepticus.16
Systemic Pathophysiology

8. Generalized convulsive status epilepticus is associated with serious systemic physiologic changes
resulting from the metabolic demands of repetitive seizures. Many of these systemic changes result from
the profound autonomic changes that occur during status epilepticus, including tachycardia, arrhythmias,
hypertension, pupillary dilation, and hyperthermia because of the massive catecholamine discharge
associated with continuous generalized seizures. Systemic changes requiring medical intervention include
hypoxia, hypercapnia, hypoglycemia, metabolic acidosis, and other electrolyte disturbances. Table
17,17-19 summarizes the physiologic changes that occur during status epilepticus.
Management of Status Epilepticus
GENERAL MEASURES
The treatment of status epilepticus involves the use of
The first step in managing status epilepticus is
potent intravenous medications that may have serious
adverse effects. Therefore, the first step in managing the assessing the patient's airway and oxygenation.
condition is to ascertain that the patient has tonic-clonic
status epilepticus, and that prolonged or repetitive seizures have occurred. A single generalized seizure
with complete recovery does not require treatment. Once the diagnosis of status epilepticus is made,
however, treatment should be initiated immediately. Necessary interventions include maintaining
oxygenation and circulation, assessing the etiology and laboratory evaluations, obtaining intravenous
access, and initiating drug therapy.
Physicians first should assess the patient's airway and oxygenation. If the airway is clear and intubation is
not immediately required, blood pressure and pulse should be checked and oxygen administered. In
patients with a history of seizures, an attempt should be made to determine whether medications have
been taken recently. A screening neurologic examination should be performed to check for signs of a
focal intracranial lesion.
Obtaining intravenous access is the next step, and blood should be sent to the laboratory for measurement
of serum electrolyte, blood urea nitrogen, glucose, and antiepileptic drug levels, as well as a toxic drug
screen and complete blood cell count. Isotonic saline infusion should be initiated. Because hypoglycemia
may precipitate status epilepticus and is quickly reversible, 50 mL of 50 percent glucose should be given
immediately if hypoglycemia is suspected. If the physician cannot check for hypoglycemia or there is any
doubt, glucose should be administered empirically. Thiamine (100 mg) should be given along with the
glucose, because glucose infusion increases the risk of Wernicke's encephalopathy in susceptible patients.
After administration of oxygen, blood gas levels should be determined to ensure adequate oxygenation.
Initially, acidosis, hyperpyrexia, and hypertension need not be treated, because these are common
findings in early status epilepticus and should resolve on their own with prompt and successful general
treatment. If seizures persist after initial measures, medication should be administered. Imaging with
computed tomography is recommended after stabilization of the airway and circulation. If imaging is
negative, lumbar puncture is required to rule out infectious etiologies.
ROLE OF ELECTROENCEPHALOGRAPHY
Electroencephalography (EEG) is extremely useful, but underutilized, in the diagnosis and management
of status epilepticus. Although overt convulsive status epilepticus is readily diagnosed, EEG can establish
the diagnosis in less obvious circumstances. Researchers in one study20 used EEG to diagnose status
epilepticus in 37 percent of patients with altered consciousness whose diagnosis was unclear on the basis
of clinical criteria. A surprising number of patients had no clinical signs of status epilepticus, and EEG
was necessary to establish the diagnosis.
EEG also can help to confirm that an episode of status epilepticus has ended, particularly when questions

9. arise about the possibility of recurrent episodes of more subtle seizures. In another study,21 investigators
monitored patients for at least 24 hours after clinical signs of status epilepticus had ended. They found
that nearly one half of their patients continued to demonstrate electrographic seizures that often had no
clinical correlation. The investigators concluded that EEG monitoring after presumed control of status
epilepticus is essential for optimal management.
Patients with status epilepticus who fail to recover rapidly and completely should be monitored with EEG
for at least 24 hours after an episode to ensure that recurrent seizures are not missed. Monitoring also is
advised if periodic discharges appear in the EEG of a patient with altered consciousness who has not had
obvious seizures. Periodic discharges in these patients suggest the possibility of preceding status
epilepticus, and careful monitoring may clarify the etiology of the discharges and allow the detection of
recurrent status epilepticus.
Pharmacologic Management
Rapid treatment of status epilepticus is crucial to prevent neurologic and systemic pathology. The goal of
treatment always should be immediate diagnosis and termination of seizures. For an anti-seizure drug to
be effective in status epilepticus, the drug must be administered intravenously to provide quick access to
the brain without the risk of serious systemic and neurologic adverse effects. Multiple drugs are
available, each with advantages and disadvantages.
BENZODIAZEPINES
The benzodiazepines are some of the most effective drugs in the treatment of acute seizures and status
epilepticus. The benzodiazepines most commonly used to treat status epilepticus are diazepam (Valium),
lorazepam (Ativan), and midazolam (Versed). All three compounds work by enhancing the inhibition of
g-aminobutyric acid (GABA) by binding to the benzodiazepine-GABA and barbiturate-receptor complex.
Diazepam. Diazepam is one of the drugs of choice for first-line management of status epilepticus.18,22-24
[References 18 and 22 through 24--Evidence level A, randomized controlled trials (RCTs)] Although the
drug enters the brain rapidly because of its high lipid solubility, after 15 to 20 minutes it redistributes to
other areas of the body, reducing its clinical effect.24,25 Despite its fast distribution half-life, the
elimination half-life is approximately 24 hours. Thus, sedative effects potentially could accumulate with
repeated administration.
Diazepam in a typical intravenous dosage of 5 to 10 mg per minute terminates seizures of any type in
about 75 percent of patients with status epilepticus.22,23,26 Adverse effects include respiratory
suppression, hypotension, sedation, and local tissue irritation. Hypotension and respiratory suppression
may be potentiated by the co-administration of other antiepileptic drugs, particularly barbiturates.
Diazepam also may be given intramuscularly and rectally (Diastat).27
Despite its pharmacokinetic and adverse effect limitations, diazepam remains an important tool in the
management of status epilepticus because of its rapid and broad-spectrum effect.
Lorazepam. Lorazepam has emerged as the preferred benzodiazepine for acute management of status
epilepticus.24 [Evidence level A, RCT] Lorazepam differs from diazepam in two important respects. It is
less lipid-soluble than diazepam, with a distribution half-life of two to three hours versus 15 minutes for
diazepam. Therefore, it should have a longer duration of clinical effect.24 Lorazepam also binds the
GABAergic receptor more tightly than diazepam, resulting in a longer duration of action. The
anticonvulsant effects of lorazepam last six to 12 hours, and the typical dose ranges from 4 to 8 mg. This
agent also has a broad spectrum of efficacy, terminating seizures in 75 to 80 percent of cases.26 Its
adverse effects are identical to those of diazepam. Thus, lorazepam also is an effective choice for acute

10. seizure management, with the added possibility of a longer duration of action than diazepam.
Midazolam. Although midazolam is rarely used as the first-choice benzodiazepine for treatment of status
epilepticus in the United States, it is used commonly in Europe. A more complete review of this agent
and its role in the treatment of status epilepticus is available elsewhere.28,29
PHENYTOIN
Phenytoin (Dilantin) is one of the most effective drugs for treating acute seizures and status epilepticus.
In addition, it is effective in the management of chronic epilepsy, particularly in patients with partial and
secondarily generalized seizures. The pharmacokinetic properties of phenytoin are reviewed
elsewhere.23,25,30
The main advantage of phenytoin is the lack of a sedating effect. However, a number of potentially
serious adverse effects may occur. Arrhythmias and hypotension have been reported, particularly in
patients older than 40 years. It is likely that these effects are associated with a more rapid rate of
administration and the propylene glycol vehicle used as its diluent. In addition, local irritation, phlebitis,
and dizziness may accompany intravenous administration.
FOSPHENYTOIN
Fosphenytoin (Cerebyx) received approval for treatment of status epilepticus from the U.S. Food and
Drug Administration (FDA) in 1996. Fosphenytoin is a water-soluble pro-drug of phenytoin that
completely converts to phenytoin following parenteral administration. Thus, the adverse events that are
related to propylene glycol are avoided. Like phenytoin, fosphenytoin is useful in treating acute partial
and generalized tonic-clonic seizures. Fosphenytoin is converted to phenytoin within eight to 15
minutes.31-34 It is metabolized by the liver and has a half-life of 14 hours. Because 1.5 mg of
fosphenytoin is equivalent to 1 mg of phenytoin, the dosage, concentration, and infusion rate of
intravenous fosphenytoin are expressed as phenytoin equivalents (PE). The initial dose of fosphenytoin is
15 to 20 mg PE per kg, so it can be infused at a rate as high as 150 mg PE per minute, a rate of infusion
that is three times faster than that of intravenous phenytoin. Intramuscular doses also can be given, but
the drug does not reach a therapeutic level for
30 minutes.35
Adverse effects that are unique to fosphenytoin include perineal paresthesias and pruritus; however, both
are related to higher rates of administration.30 Unlike phenytoin, fosphenytoin does not cause local
irritation. Intravenous therapy has been associated with hypotension, so continuous cardiac and blood
pressure monitoring are recommended. Although fosphenytoin represents an improvement over
traditional phenytoin, it is expensive, and some hospital formulary committees are unwilling to pay the
difference.18
PHENOBARBITAL
Phenobarbital typically is used after a benzodiazepine or phenytoin has failed to control status
epilepticus. The normal loading dose is 15 to 20 mg per kg. Because high-dose phenobarbital is sedating,
airway protection is an important consideration, and aspiration is a major concern. Intravenous
phenobarbital also is associated with systemic hypotension. Although phenobarbital can be loaded fairly
rapidly, a full therapeutic dose may take 30 minutes to infuse. It is diluted in 60 to 80 percent propylene
glycol, which is associated with a number of complications, including renal failure, myocardial
depression, and seizures.22,25 These limitations relegate phenobarbital to use in patients who have not
responded to other agents.
VALPROATE

11. The FDA approved valproate (Depacon) for use in 1997.36 Parenteral valproate is used primarily for
rapid loading and when oral therapy is impossible. It has a broad spectrum of efficacy and may be useful
in patients with absence or myoclonic status epilepticus. Adverse effects include local irritation,
gastrointestinal distress, and lethargy. This drug is not FDA-approved for the treatment of status
epilepticus.
Choice of Antiepileptic Drug
Although there is no ideal drug for treatment of status
Most authors agree that lorazepam or
epilepticus, a number of considerations influence the
diazepam therapy should be initiated first in
choice of antiepileptic drug for this condition. Table 2
summarizes dosages, pharmacology, and adverse effects the treatment of status epilepticus, followed by
phenytoin.
of medications used to manage status epilepticus and
refractory status epilepticus. Comparative studies of
treatments are few, but consensus has emerged concerning initial medications. Most authors agree that
lorazepam or diazepam should be initiated, followed by phenytoin. The evidence for these choices is
summarized below.
DIAZEPAM VS. LORAZEPAM
In one trial,26 intravenous lorazepam was compared with diazepam as first-line treatment for status
epilepticus. This randomized, double-blind trial, which included all types of status epilepticus, enrolled
78 patients who received 10 mg of diazepam or 4 mg of lorazepam by intravenous injection over two
minutes. There were no significant differences in efficacy or latency of action between the drugs, but the
number of patients was too small to determine true significance. Seizures were terminated in 58 percent
of patients receiving diazepam compared with 78 percent of patients treated with lorazepam. Diazepam
had a median latency of two minutes (range: immediate to 10 minutes) versus a median latency of three
minutes with lorazepam (range: immediate to 15 minutes).26

12. TABLE 2
Antiepileptic Drugs Used in Status Epilepticus
Dialyzable
Loading Maintenance Route of (% protein
Drug dose dosage metabolism binding) Adverse effects
Diazepam 10 to 20 mg None Hepatic >90 Respiratory
(Valium) depression,
hypotension,
sialorrhea
Lorazepam 4 mg None Hepatic 90 Same as
(Ativan) diazepam
Phenytoin 18 to 20 mg 5 mg per kg per Hepatic 70 Cardiac
(Dilantin) per kg at 50 day depression,
mg per hypotension
minute
Fosphenytoin 18 to 20 mg None Hepatic 70 Cardiac
(Cerebyx) per kg PE at depression,
150 mg per hypotension,
minute paresthesias
Phenobarbital 20 mg per 1 to 4 mg per kg Hepatic 50 to 60 Respiratory
kg per hour suppression
Pentobarbital 2 to 8 mg 0.5 to 5 mg per kg Hepatic 59 to 63 Hypotension,
per kg per hour respiratory
suppression
Midazolam 0.2 mg per 0.75 to 10 mg per Hepatic 96 Hypotension,
(Versed) kg kg per minute respiratory
suppression
Propofol 2 mg per kg 5 to 10 mg per kg Hepatic 97 to 98 Respiratory
(Diprivan) per hour initially, depression,
then 1 to 3 mg per hypotension,
kg per hour lipemia,acidosis
PE = phenytoin equivalents.

13. Status Epilepticus
1. Definition
Conventional definition: >30 min of continuous seizure or convulsions or of intermittent seizures without
full recovery.
There is evidence that seizures of 30 minutes or longer duration cause neuronal damage, and this is the
basis for the definition. However, do not wait for brain damage to occur--treat for status epilepticus if the
seizure has lasted more than 5 to 10 minutes.
2. Classification of status
Generalized
•
• Convulsive
Nonconvulsive
•
• Absence
Late stage of convulsive
•
Partial
•
• Simple
Complex
•
Generalized motor status is a true medical emergency
3. Stages of status epilepticus
1. Discrete seizures
2. Merging seizures
3. Continuous ictal activity
4. Continuous ictal activity, punctuated by low voltage flat activity
5. Periodic epileptiform discharges on a quiet background
(Treiman et al. 1990)
4. Systemic complications of status
Lactic acidosis
•
Hypo- or hyperglycemia
•
Hyperpyrexia
•
Dehydration
•
Shock
•
Rhabdomyolysis
•
Death
•
5. Mortality of status epilepticus
Dead of status 1.8%
•
Dead of underlying cause 28.8%
•

14. Dead other causes 6.5%
•
Alive 63.1%
•
6. Mortality of status epilepticus
A
comparison
of survival
by duration
in status
epilepticus
shows a
marked
increase in
mortiality
for patients
in
prolonged
status
epilepticus.
(Towne et
al. 1994)
7. Neuronal death
Cerebral cortex (laminar necrosis)
•
Hippocampus
•
Amygdala
•
Thalamus
•
Cerebellum
•
8. Epilepsy
Status epilepticus can produce epilepsy.
•
20 to 40% of persons develop epilepsy after an episode of status epilepticus. (Hesdorffer et al.
•
1998)
The mechanism of this could be damage to hippocampus.
•
9. Important!!
Eliminate the electrical seizure to prevent neuronal injury in status epilepticus
10. Steps in treatment
1. ABC's
2. Quick assessment

15. 3. Stop the seizure
4. Find the cause
11. Quick assessment
History: seizures?
stroke?
head trauma?
neoplasm?
medical noncompliance?
alcohol or barbiturate use?
theophylline use?
Examination: fever?
papilledema?
elevated blood pressure?
focal seizure onset?
focal neurologic exam?
12. Causes of status
Medication withdrawal 22.5%
CVA 22.5%
Alcohol withdrawal 14.2%
Idiopathic 14.2%
Anoxia 11.9%
Metabolic disorder 11.5%
Hemorrhage 5.1%
Infection 5.1%
Tumor 4.4%
Trauma 4.0%
Drugs 2.4%
CNS infection 0.8%
Congenital brain injury 0.8%
Some patients have more than one etiology.
(Towne et al. 1994)
13. Laboratory studies often useful
Blood glucose, sodium, calcium, magnesium, creatinine, BUN, ABG, anticonvulsant levels
•
CBC, CPK, toxicology screen
•
CT scan w/o contrast
•
Lumbar puncture
•
EEG
•
14. Simple procedures always recommended
Pulse oximetry
•
Continuous ECG
•
IV
•

16. 15. Initial Rx for seizures
If hypoglycemic, then:
1. IV glucose (50 cc D50)
2. Thiamine (10 mg IV + 90 mg IM)
16. Anticonvulsants
Standard:
•
• Lorazepam
Diazepam
Fosphenytoin
Phenytoin
Phenobarbital
Useful:
•
• Valproate
Midazolam
17. Benzodiazepines
Use a benzodiazepine first. They work quickly, and status epilepticus is more difficult to control
•
if treatment is delayed.
Lorazepam 4 - 8 mg (0.1 mg/kg) IV
•
• Slower onset, longer duration
Diazepam 5 - 20 mg (0.15 - 0.25 mg/kg) IV
•
• Rapid onset, short duration
Give IV push
•
Be prepared to intubate
•
IV diazepam is not useful for serial seizures
•
18. Diazepam has a short duration of action
Diazepam has only a
short duration of action.
This is primarily
because it quickly
redistributes from brain
to fat. Note that plasma
diazepam concentration
is less than half its peak
ten minutes after an IV
infusion.
(Ramsay et al. 1979)

17. 19. Phenytoin
Loading dose 18 - 20 mg/kg IV (1000 - 2000 mg)
•
Rate < 50 mg/min. to avoid hypotension, arrhythmias
•
Never give IM
•
Never in dextrose
•
Loading dose works up to 18 hours
•
Stops 80% of generalized motor status epilepticus
•
20. Fosphenytoin
Prodrug of phenytoin for
•
parenteral administration
Rapidly and completely
•
converted to phenytoin by
nonspecific tissue
phosphatases
Water soluble, pH 8.6 - 9
•
Can be given IM
•
No sterile necrosis or tissue
•
abscesses
Molecular weight 1.5 times
•
that of phenytoin
21. IV loading of fosphenytoin
Fosphenytoin is rapidly converted to phenytoin.
Plasma concentrations of phenytoin are essentially
identical whether phenytoin or fosphenytoin is
infused.
22. Phenobarbital
Loading dose 20 mg/kg IV
•
Not > 100 mg/min
•
Patient should be intubated
•
23. Intravenous valproic acid
Depacon®
•
Give an IV loading dose followed by a three times daily dose of valproic acid by mouth or IV.
•
Package insert says not faster than 50 mg/min (but I have given it up to 200 mg/min, and this is
•
probably safe).
24. Serial seizures
Fosphenytoin IV or IM
•
Phenytoin PO
•

18. Lorazepam IV or PO
•
Oral antiepileptic drugs
•
Diazepam rectal gel
•
Not IV diazepam
•
25. Refractory status: midazolam
Give midazolam as a continuous infusion
•
Use EEG monitoring if possible, titrate infusion to eliminate electrographic seizures.
•
200 micrograms/kg as a slow IV bolus, followed by 0.75 to 10 micrograms/kg/min.
•
In the most refractory cases more than 10 micrograms/kg/min may be needed.'
•
Hypotension is uncommon but may occur.
•
26. Refractory status: pentobarbital
Administer pentobarbital as a continuous infusion.
•
5 mg/kg load, then 1-3 mg/kg/hour
•
Must use EEG monitoring; goal is to titrate drug infusion to EEG burst suppression.
•
Hypotension is common; fluids and pressors may be needed.
•
27. EEG burst suppression
A quiet EEG background is frequently interrupted by bursts of high voltage activity.
The high voltage activity often contains epileptiform spikes or spike-wave discharges.
28. Other types of status epilepticus
Generalized nonconvulsive status epilepticus
•
• May be a late stage of convulsive status epilepticus
Signs may be subtle: subtle facial twitching, nystagmus, ocular deviation
•
Myoclonic status epilepticus
•
• May follow anoxic encephalopathy
May be stimulus-sensitive
•
29. Controversies in status epilepticus
Significance of certain EEG patterns:
•
• Periodic epileptiform discharges (PLEDs)
Bi-PLEDs
•
Periodic discharges
•
Frequent triphasic waves
•
Titrate IV antiepileptic with EEG to:
•
• Burst suppression
• Easy to see, but may go flat before burst suppression
• Elimination of seizure
• Sometimes hard to recognize

19. 30. Periodic discharges
This patient had right frontal periodic discharges and encephalopathy. Treatment with fosphenytoin and valproate
improved the discharges, but the patient was clinically unimproved.
31. Time table for treatment of status
a. 0-10 min, do ABC's:
O2 by nasal cannula. Intubate if necessary.
•
Establish IV access.
•
Draw glucose, serum chemistries, CBC, toxicology screen.
•
Draw antiepileptic drug levels if patient known to be treated.
•
Thiamine (100 mg) then glucose (50 ml of 50%) if hypoglycemia demonstrated or suspected.
•
b. 10-20 min, administer a benzodiazepine drug:
Lorazepam (0.1 mg/kg at 2 mg/min IV) or diazepam (0.2 mg/kg at 5 mg/min IV). Lorazepam is the drug
of choice. Both drugs act quickly, diazepam slightly faster, but it redistributes to fat quickly, and its
effective duration of action may be only 5-10 min. With diazepam, repeated doses are often necessary. If
diazepam is used, phenytoin (or fosphenytoin) should next be given to prevent recurrence of seizures.
The effective duration of action of lorazepam is 8-10 hours, and is recommended for initial treatment of
status epilepticus.
c. 20-60 min, administer fosphenytoin or phenytoin
Fosphenytoin is a water-soluble phosphate pro-drug of phenytoin. It replaces IV phenytoin, which is
highly alkaline (pH 12) and dissolved in 40% propylene glycol/10% ethanol. It can be dosed using
quot;phenytoin equivalentsquot;. (Its molecular weight is 1.5 times that of phenytoin.) Can be used IM. Can be
given at a rate of 150 mg/min IV. Hypotension and cardiac arrhythmias are less common than with
phenytoin.
Phenytoin In adults give 18 mg/kg no faster than 50 mg/min IV. Monitor ECG and BP during infusion.
Do not use glucose-containing IV solution. Purge IV line with normal saline before infusion. Do not give
phenytoin IM because it may cause sterile abscesses. Ensure adequate IV access because local infiltration
of phenytoin can cause skin necrosis.
d. >60 min
Administer additional doses of fosphenytoin or phenytoin up to a maximum of 30 mg/kg.
•
Administer phenobarbital (20 mg/kg at 100 mg/min IV). Assisted ventilation will usually be
•
required.
e. If seizures persist:
Pentobarbital infusion. 5 mg/kg load, then 1-3 mg/kg/hr. Must use EEG monitoring, goal is to
•
titrate to EEG burst-suppression. Avoid hypotension if possible, but fluids and pressors may be
needed.
Midazolam drip. Use with EEG monitoring if possible, titrate infusion to eliminate electrographic
•

20. seizures. 200 micrograms/kg as a slow IV bolus, followed by 0.75 to 10 micrograms/kg/min
continuous infusion. In the most refractory cases more than 10 micrograms/kg/min may be
needed. Hypotension is uncommon but may occur.
Propofol drip. Few advantages over pentobarbital.
•
General anesthesia (isoflurane, ketamine).
•
Paraldehye: no longer available.
•
Diazepam drip. Used infrequently.
•
Lidocaine drip. Used infrequently. May exacerbate seizures.
•
Do not merely paralyze the patient.
•

22. Seizures (convulsions) are the result of uncontrolled electrical discharges from the nerve cells of the
cerebral cortex and are characterized by sudden, brief attacks of altered consciousness, motor activity,
and/or sensory phenomena.
Seizures can be associated with a variety of cerebral or systemic disorders as a focal or generalized
disturbance of cortical function. Sensory symptoms arise from the parietal lobe; motor symptoms arise
from the frontal lobe.
The phases of seizure activity are prodromal, aural, ictal, and postictal. The prodromal phase involves
mood or behavior changes that may precede a seizure by hours or days. The aura is a premonition of
impending seizure activity and may be visual, auditory, or gustatory. The ictal stage is characterized by
seizure activity, usually musculoskeletal.
The postictal stage is a period of confusion/somnolence/irritability that occurs after the seizure.
The main causes for seizures can be divided into six categories:
Toxic agents: Poisons, alcohol, overdoses of prescription/nonprescription drugs (with drugs the leading
cause).
Chemical imbalances: Hyperkalemia, hypoglycemia, and acidosis.
Fever: Acute infections, heatstroke.
Cerebral pathology: Resulting from head injury, infections, hypoxia, expanding brain lesions, increased
intracranial pressure.
Eclampsia: Prenatal hypertension/toxemia of pregnancy.
Idiopathic: Unknown origin.
Seizures can be divided into two major classifications (generalized and partial). Generalized seizure types
include tonic-clonic, myoclonic, clonic, tonic, atonic, and absence seizures. Partial (focal) seizures are the
most common type and are categorized as either (1) simple (partial motor, partial sensory) or (2)
complex.
CARE SETTING
Community; however, may require brief inpatient care on a medical or subacute unit for
stabilization/treatment of status epilepticus.
RELATED CONCERNS
Cerebrovascular accident (CVA)/stroke
Craniocerebral trauma (acute rehabilitative phase)
Psychosocial aspects of care

23. Substance dependence/abuse rehabilitation
Patient Assessment Database
ACTIVITY/REST
May report: Fatigue, general weakness
Limitation of activities/occupation imposed by self/significant other (SO)/healthcare provider or others
May exhibit: Altered muscle tone/strength
Involuntary movement/contractions of muscles or muscle groups (generalized tonic-clonic seizures)
CIRCULATION
May exhibit: Ictal: Hypertension, increased pulse, cyanosis
Postictal: Vital signs normal or depressed with decreased pulse and respiration
EGO INTEGRITY
May report: Internal/external stressors related to condition and/or treatment
Irritability; sense of helplessness/hopelessness
Changes in relationships
May exhibit: Wide range of emotional responses
ELIMINATION
May report: Episodic incontinence
May exhibit: Ictal: Increased bladder pressure and sphincter tone
Postictal : Muscles relaxed, resulting in incontinence (urinary/fecal)
FOOD/FLUID
May report: Food sensitivity nausea/vomiting correlating with seizure activity
May exhibit: Dental/soft-tissue damage (injury during seizure)
Gingival hyperplasia (side effect of long-term phenytoin [Dilantin] use)
NEUROSENSORY
May report: History of headaches, recurring seizure activity, fainting, dizziness

24. History of head trauma, anoxia, cerebral infections
Prodromal phase: Vague changes in emotional reactivity or affective response preceding aura in some
cases and lasting minutes to hours
Presence of aura (stimulation of visual, auditory, hallucinogenic areas)
Postictal: Weakness, muscle pain, areas of paresthesia/paralysis
May exhibit: Seizure characteristics: (ictal, postictal)
Generalized seizures:
Tonic-clonic (grand mal): Rigidity and jerking posturing, vocalization, loss of consciousness, dilated
pupils, stertorous respiration, excessive salivation (froth), fecal/urinary incontinence, and biting of the
tongue may occur and last 2–5 min.
Postictal phase: Patient sleeps 30 min to several hours, then may be weak, confused, and amnesic
concerning the episode, with nausea and stiff, sore muscles
Myoclonic: Short abrupt muscle contractions of arms, legs, torso; may not be symmetrical; lasts seconds
Clonic: Muscle contraction with relaxation resembling myoclonic movements but with slower
repetitions; may last several minutes
Tonic: Abrupt increase in muscle tone of torso/face, flexion of arms, extension of legs; lasts seconds
Atonic: Abrupt loss of muscle tone; lasts seconds; patient may fall
Absence (petit mal): Periods of altered awareness or consciousness (staring, fluttering of eyes) lasting 5–
30 sec, which may occur as many as 100 times a day; minor motor seizures may be akinetic (loss of
movement), myoclonic (repetitive motor contractions), or atonic (loss of muscle tone). Postictal phase:
Amnesia for seizure events, no confusion, able to resume activity
Status epilepticus: Defined as 30 or more minutes of continuous generalized seizure activity or two or
more sequential seizures without full recovery of consciousness in between, possibly related to abrupt
withdrawal of anticonvulsants and other metabolic phenomena. If absence seizures are the pattern,
problem may go undetected for a period of time because patient does not lose consciousness
Partial seizures:
Complex (psychomotor/temporal lobe): Patient generally remains conscious, with reactions such as
dream state, staring, wandering, irritability, hallucinations, hostility, or fear. May display involuntary
motor symptoms (lip smacking) and behaviors that appear purposeful but are inappropriate (automatism)
and include impaired judgment and, on occasion, antisocial acts; lasts 1–3 min. Postictal phase: Absence
of memory for these events, mild to moderate confusion
Simple (focal-motor/Jacksonian): Often preceded by aura (may report deja vu or fearfulfeeling); no loss

25. of consciousness (unilateral) or loss of consciousness (bilateral); convulsive movements and temporary
disturbance in part controlled by the brain region involved (e.g., frontal lobe [motor dysfunction], parietal
[numbness, tingling], occipital [bright, flashing lights], posterotemporal [difficulty speaking]).
Convulsions may march along limb or side of body in orderly progression. If restrained during seizure,
patient may exhibit combative and uncooperative behavior; lasts seconds to minutes
PAIN/DISCOMFORT
May report: Headache, muscle/back soreness postictally
Paroxysmal abdominal pain during ictal phase (may occur during some partial/focal seizures without loss
of consciousness)
May exhibit: Guarding behavior
Alteration in muscle tone
Distraction behavior/restlessness
RESPIRATION
May exhibit: Ictal: Clenched teeth, cyanosis, decreased or rapid respirations; increased mucous secretions
Postictal: Apnea
SAFETY
May report: History of accidental falls/injuries, fractures
Presence of allergies
May exhibit: Soft-tissue injury/ecchymosis
Decreased general strength/muscle tone
SOCIAL INTERACTION
May report: Problems with interpersonal relationships within family/socially
Limitation/avoidance of social contacts
TEACHING/LEARNING
May report: Familial history of epilepsy
Drug (including alcohol) use/misuse
Increased frequency of episodes/failure to improve

26. Discharge plan
DRG projected mean length of inpatient stay: 4.4 days
May require changes in medications, assistance with some homemaker/maintenance tasks relative to
issues of safety, and transportation
Refer to section at end of plan for postdischarge considerations.
DIAGNOSTIC STUDIES
Electrolytes: Imbalances may affect/predispose to seizure activity.
Glucose: Hypoglycemia may precipitate seizure activity.
Blood urea nitrogen (BUN): Elevation may potentiate seizure activity or may indicate nephrotoxicity
related to medication regimen.
Complete blood count (CBC): Aplastic anemia may result from drug therapy.
Serum drug levels: To verify therapeutic range of antiepileptic drugs (AEDs).
Toxicology screen: Determines potentiating factors such as alcohol or other drug use.
Skull x-rays: Identifies presence of space-occupying lesions, fractures.
Electroencephalogram (EEG) may be done serially: Locates area of cerebral dysfunction; measures brain
activity.
Brain waves take on characteristic spikes in each type of seizure activity; however, up to 40% of seizure
patients have normal EEGs because the paroxysmal abnormalities occur intermittently.
Video-EEG monitoring, 24 hours (video picture obtained at same time as EEG): May identify exact focus
of seizure activity (advantage of repeated viewing of event with EEG recording).
Computed tomography (CT) scan: Identifies localized cerebral lesions, infarcts, hematomas, cerebral
edema, trauma, abscesses, tumor; can be done with or without contrast medium.
Magnetic resonance imaging (MRI): Localizes focal lesions.
Positron emission tomography (PET): Demonstrates metabolic alterations, e.g., decreased metabolism of
glucose at site of lesion.
Single photon emission computed tomography (SPECT): May show local areas of brain dysfunction
when CT and MRI are normal.
Magnetoencephalogram: Maps the electrical impulses/potential of brain for abnormal discharge patterns.
Lumbar puncture: Detects abnormal cerebrospinal fluid (CSF) pressure, signs of infections or bleeding

27. (i.e., subarachnoid, subdural hemorrhage) as a cause of seizure activity (rarely done).
Wada’s test: Determines hemispheric dominance (done as a presurgical evaluation before temporal
lobectomy).
NURSING PRIORITIES
1. Prevent/control seizure activity.
2. Protect patient from injury.
3. Maintain airway/respiratory function.
4. Promote positive self-esteem.
5. Provide information about disease process, prognosis, and treatment needs.
DISCHARGE GOALS
1. Seizures activity controlled.
2. Complications/injury prevented.
3. Capable/competent self-image displayed.
4. Disease process/prognosis, therapeutic regimen, and limitations understood.
5. Plan in place to meet needs after discharge.