Status epilepticus can occur in patients with a history of seizures
or can be the first epileptic event. The most common causes of status
epilepticus include subtherapeutic antiepileptic levels; preexisting
neurologic conditions, such as prior CNS infection, trauma, hemorrhage,
or stroke; acute stroke; anoxia or hypoxia; metabolic abnormalities;
and alcohol or drug withdrawal.15
Types of Seizure
Status epilepticus is continuous or intermittent seizures
for more than 5 minutes without recovery of consciousness.16,17 This
is a reasonable working definition, because after 5 minutes of continuous
activity, seizures become less likely to spontaneously terminate,
less likely to be controlled with antiepileptic drugs, and more likely
to cause neuronal damage. Therefore, treatment for status
epilepticus should be initiated in all patients with continuous
seizure activity lasting more than 5 minutes.
Animal models suggest that permanent neurologic damage could
occur after 20 or more minutes of seizure activity. After 20 or
30 minutes, hypotension, hypoxia, metabolic acidosis, hyperthermia,
and hypoglycemia can develop. Neurotoxic excitatory amino acids
and calcium are released into cells. Cardiac dysrhythmias, rhabdomyolysis,
and pulmonary edema can develop.18
In nonconvulsive status epilepticus, the patient is comatose
or has fluctuating abnormal mental status or confusion, but no overt
seizure activity or only subtle activity. The diagnosis is challenging
and is typically made by EEG. Findings suggestive of nonconvulsive
status epilepticus include a prolonged post-ictal period after a
generalized seizure; subtle motor signs such as twitching, blinking,
and eye deviation; fluctuating alterations in mental status; or
unexplained stupor or confusion in the elderly.18
Epilepsia partialis continua is focal tonic-clonic seizure activity
with normal alertness and responsiveness. The distal leg and arm
are most commonly affected.
The goal of treatment is seizure control as soon as possible,
and within 30 minutes of presentation (Figure
165-1). Examination, identification of precipitating cause,
application of the ABCs, and treatment begin simultaneously.
Guidelines for management of status epilepticus. ABG = arterial
blood gases; AED = antiepileptic drug; CBC = complete
blood count; PE = phenytoin equivalent.
A brief history and physical examination should be directed toward
discovery of the cause of the seizures and to any injury that may
have resulted. Any of the causes of seizures (Table
165-2) may result in status epilepticus. In many patients,
no specific cause is found.
A large-bore IV line should be established and a bedside glucose
determination made. Administration of an IV fluid without glucose
will facilitate administration of anticonvulsant drugs (glucose
is not compatible with phenytoin). The patient should be placed
on oxygen, a cardiac monitor, and a pulse oximeter. If capnometry
is available, that should be applied.
Endotracheal intubation is recommended when status epilepticus
is diagnosed. If a paralytic agent is used to assist with intubation,
a short-acting agent should be used so the physician can monitor
ongoing seizure activity.
Initial laboratory evaluation should include blood glucose, a
metabolic panel including calcium and magnesium, and if appropriate,
a pregnancy test, a toxicology screen, and anticonvulsant levels.
Glucose should be administered IV if hypoglycemia is suspected
or confirmed. There is no benefit to giving additional glucose to
normoglycemic patients. Rectal temperature should be monitored,
and hyperthermia should be treated with passive cooling. A urinary
drainage catheter should be placed to monitor urine output and a
nasogastric tube to minimize aspiration.
If toxic ingestion is suspected as the cause of seizures, GI
decontamination (as appropriate) should ensue. Emergency lumbar
puncture should not be attempted during status epilepticus. If
bacterial meningitis is suspected, empiric antibiotic therapy should
be started. Status epilepticus can induce a brief peripheral
leukocytosis as well as a mild cerebrospinal fluid pleocytosis.
Radiographic studies (such as a CT scan) will usually need to be
delayed until the seizures are controlled.
Drugs in Status Epilepticus
The drugs most often used in the therapy of status epilepticus
are the benzodiazepines (lorazepam, or if not available, diazepam)
and phenytoin or fosphenytoin (Figure 165-1).
Benzodiazepines are used in patients with continuous or very
frequent seizures to temporarily control the seizures until more
specific agents can be given. IV lorazepam (4 milligrams)
and IV diazepam (5 to 10 milligrams) have equal efficacy in controlling
status epilepticus.17 Compared to diazepam, lorazepam
has a slightly slower onset (3 vs. 2 minutes), but significantly
longer duration of action (12 to 24 hours vs.15 to 60 minutes),
and is associated with fewer seizure recurrences. Thus, lorazepam
is considered the initial agent of choice. Lorazepam is also
more effective than phenytoin or phenobarbital as the initial drug.19 Respiratory
depression and hypotension may occur, especially in young children
and in patients who have taken alcohol, barbiturates, narcotics,
or other sedatives. In patients with difficult IV access and emergent
need for seizure control, there may be a role for rectal diazepam
gel or buccal midazolam. Although there have been no such trials
in adults, rectal
diazepam gel has been used by EMS providers in children with good
success for years, and recent trials of buccal midazolam (0.5 milligram/kg,
up to 10 milligrams) show more efficacy than rectal diazepam in
terminating seizure activity in children.20,21
In status epilepticus, benzodiazepines are followed by longer-acting
antiepileptics, commonly phenytoin. The recommended loading dose
is 20 milligrams/kg IV. Doses well in excess of the usual
1000 milligrams are required for many adults. If necessary and tolerated,
up to 30 milligrams/kg (“high dose” phenytoin)
can be delivered. A smaller loading dose (15 milligrams/kg)
may be used in the elderly, but the loading dose is not reduced
in patients with renal or hepatic disease. Due to myocardial depression
effects from its propylene glycol diluent, phenytoin is typically infused
no faster than at a rate of 25 milligrams per minute. However, the rate
may be increased to 50 milligrams per minute during status epilepticus.
Patients should be placed on a cardiac monitor, with blood pressure
assessments every 5 to 15 minutes during the infusion and every
15 minutes for 1 hour postinfusion.22 Phenytoin
should not be mixed with any glucose-containing IV fluid and should
not be given IM due to erratic absorption. The drug is contraindicated
in the presence of second- or third-degree atrioventricular block.
Adverse effects include significant infusion-site reactions, hypotension,
and cardiac dysrhythmias, so continuous cardiac monitoring is needed.
If side effects develop, the infusion should be stopped and may
be restarted at a lower rate when the side effects have resolved.
In some cases, patients are unable to tolerate the drug.
Fosphenytoin is a water-soluble prodrug of phenytoin that is
converted to phenytoin in the plasma. In status epilepticus, fosphenytoin
has similar time of onset, effectiveness, and cardiac effects as
phenytoin. Its advantages include fewer infusion-site reactions
due to the lack of propylene glycol and ethanol as the diluents.
Second, fosphenytoin may be infused at a faster rate. Fosphenytoin
dosing is expressed as “phenytoin equivalents” to
prevent confusion. The loading dose is 20 milligrams phenytoin equivalent
per kg, which can be infused at 150 milligrams phenytoin equivalent
per minute. Additionally, unlike phenytoin, fosphenytoin can be
given IM, which may be useful if the patient does not have IV access.
Refractory status epilepticus is defined as persistent seizure
activity despite the IV administration of adequate amounts of two
antiepileptic agents. The standard regimens of benzodiazepines and
phenytoin are sufficient to control status epilepticus within 30
minutes of presentation in most patients. In some (generally patients
with structural lesions, anoxic injuries, metabolic encephalopathy,
or CNS infections), seizures continue for >60 minutes despite first-
and second-line treatment. In one study, 31% of patients
with status epilepticus developed refractory status epilepticus.23
Various approaches to refractory status epilepticus have been
advocated (Figure 165-1).24–30 Overall,
there are few controlled trials that strongly support a single agent.
Ideally, these modalities are used in an intensive care setting,
as advanced respiratory and cardiovascular support, as well as continuous
EEG and invasive hemodynamic monitoring, may be needed. Consultation
from an anesthesiologist and neurologist should be obtained.
IV valproate has been advocated as a treatment modality.15,24,25 It
is well tolerated with few side effects. Loading dose recommendations
vary from 20 to 30 milligrams/kg, with infusion over 2
to 12 minutes.26
Case reports suggest that IV levetiracetam, 1000 milligrams,
may be effective in refractory status epilepticus.26
Barbiturates, such as phenobarbital (up to 20 milligrams/kg
IV) or pentobarbital, may be considered as third-line drugs in patients
who are unable to tolerate phenytoin or in patients whose seizures
are not controlled despite full loading doses of benzodiazepines
and phenytoin. However, patients who do not respond to lorazepam
and phenytoin may not respond to barbiturates. A study by
Mayer23 found no added seizure control with phenobarbital.
A meta-analysis27 showed improved seizure control
with pentobarbital compared to propofol or midazolam, but no difference
in mortality. Respiratory depression and hypotension are common
when using barbiturates, especially at higher doses or when diazepam or
lorazepam is also given.
Anesthesia may be induced to treat refractory status epilepticus
by administering infusions of midazolam or propofol for 12 to 24
hours. Midazolam and propofol have the advantage over barbiturates
of having a short half-life and rapid clearance, allowing for earlier
extubation and earlier clinical assessment; midazolam also causes
Ketamine may be considered as an agent of last resort, as it
has neuroprotective properties and has proven effective in experimental
models. Its major contraindication is the presence of intracranial
masses, as ketamine raises intracranial pressure.31–33
Neuromuscular blocking agents (usually pancuronium or vecuronium) are
sometimes helpful. These drugs will abolish tonic-clonic movements and
may facilitate ventilation and other measures, but they have no
effect on abnormal neuronal activity. EEG monitoring is mandatory
to assess the effectiveness of anticonvulsant therapy when neuromuscular blockers