Case Presentation
A 37-year
old male is brought to the emergency department by EMS because of
a seizure at home upon awakening. The patient had a generalized tonic-clonic
seizure that lasted several minutes and spontaneously resolved, followed
by a period of unresponsiveness during EMS transport. The patient
is known to have a history of post-traumatic seizures that are managed
with phenytoin and phenobarbital. The family stated that the patient
has had neither recent illness nor head trauma. The family stated
that they believed the patient was compliant with his medications,
although non-compliance has been an issue in the past.
In the Emergency Department,
the patient begins to respond to questions, but is still somewhat
post-ictal. On initial exam, there are neither focal neurological
findings nor any evidence of any other medical condition that would
precipitate a seizure. The patient then has another generalized seizure
with tonic-clonic seizure activity. The seizure lasts several minutes
while medications were being obtained.
Key Learning Points
1. There is good data to
support the initial use of benzodizepines in ED patients with seizures
and SE. Both lorazepam and diazepam are useful IV agents, with slightly
different characteristics that guide ED use.
2. The phenytoins are a
useful second agent for use in ED SE patients. Factors such as the
need for a rapid infusion, safety, the need for IM use, and cost will
guide the ED physician in selecting fosphenytoin over phenytoin. Both
may be useful in doses up to 30 mg/kg in SE patients.
3. Phenobarbital and valproate
may be useful for the treatment of ED SE patients who are refractory
to the benzodiazepines and phenytoins, as well as in pediatric patients.
4. Propofol can be utilized
to achieve burst suppression in refractory SE patients, as can an
IV midazolam infusion.
TOP
Emergency
Department Management of Patients with
Seizures and SE:
The Role of Therapies Utilized
After Initial Benzodiazepine Therapy
Introduction
Epidemiology:
What percent of ED patient present because of seizure disorders?
What percent of ED seizure patients will not respond to initial treatment
with benzodiazepines? Does efficacy differ between diazepam and lorazepam?
Conclusions:
1. Up to 2% of all ED patients will present because a seizure
disorder.
2. 5-17% of all seizure patients will seize while in the Emergency
Department.
3. 6% of ED patients will be classified as having SE.
4. Lorazepam is expected to terminate seizures and SE in 59-89%
of patients
5. Diazepam is expected to terminate seizures and SE in 43-76%
of patients.
6. The use of lorazepam in pediatric patients with seizures and
SE is associated with fewer pulmonary complications than is the use
of diazepam.
Comments:
There
is reasonable data regarding the epidemiology of seizures in the ED. The data regarding which initial benzodiazepine suggests that
lorazepam may be preferable in the most critically ill patients (those
with prolonged SE) and in children.
The use of lorazepam, however, may render the SE patient for
a longer period of time, possibly requiring prolonged observation
at a higher level of care. This
may be important when considering the use of lorazepam as opposed
to diazepam in ED SE patients.
What
is the role of the following second line therapies in SE patients:
IV phenytoins? IV phenobarbital? IV valproate? IV propofol?
IV
Phenytoins Conclusions:
1. The combination of diazepam and phenytoin will terminate between
38 and 56% of seizures in patients
with SE.
2. No published articles demonstrate any enhanced efficacy of
fosphenytoin over phenytoin.
3. One case series suggests that high dose phenytoin may be useful
in SE patients.
4. The Epilepsy Foundation of America Consensus Guideline suggests
that high dose phenytoins may be effective in treating SE.
Comments:
Fosphenytoin
may be useful in SE since it can be rapidly infused.
It is intuitively obvious that fosphenytoin should be safer
that phenytoin, since fosphenytoin is water-soluble and can be given
IM when clinically indicated.
Despite the publication of abstracts that suggest the greater
safety of fosphenytion, there have been no publications in the Emergency
Medicine literature of these safety data.
Once published, these fosphenytoin articles may allow for stronger
recommendations to be made regarding its use in ED SE patients.
IV
Phenobarbital Conclusions:
1. Phenobarbital is comparable to the use of diazepam in phenytoin
in the termination of seizures and SE.
2. 43-61% of patients with seizures and SE are effectively with
phenobarbital.
3. When used with phenytoin, phenobarbital will effectively treat
57-62% of seizures and SE.
Comments:
Although
phenobarbital is a useful drug in the treatment of SE, it is less
often used because it must be given slowly
in
order to avoid respiratory depression.
Despite this caveat, it is an effective drug that should be
considered in
any
SE patient refractory to initial therapies.
IV
Valproate Conclusions:
1. Valproate will control SE in 58-83% of patients.
2. IV valproate has been shown to be infused without hypotension
in geriatric patients and at rapid rates in pediatric patients.
Comments:
IV
valproate may be preferred over the phenytoins in ED patients with
absence SE. It may also be useful in other SE patients, but there are no
well-controlled US studies that confirm this potential use.
Because it can be rapidly infused, it may be useful in SE patients
after the use of the benzodiazepines and phenytoins.
It also may be preferred over drugs such as phenobarbital or
propofol because it has fewer cardiopulmonary effects that these drugs.
IV
Propofol Conclusions:
1. The use of propofol provides a 63-64% efficacy in treating
SE patients.
2. Propofol may be less effective than high-dose barbiturates,
and comparable to the use of midazolam in the
treatment of SE patients.
3. Propofol may be associated with a higher mortality than the
use of midazolam in more critically ill patients.
Comments:
Proprofol
is a drug that is used in the in ED most often when intubation is
required because of respiratory failure in otherwise relatively awake
patients, such as in young status asthmaticus patients.
It appears to provide burst suppression as does pentobarbital,
but has fewer cardiopulmonary complications and can be utilized more
easily in the ED. The
studies suggest that an IV midazolam drip is another drug that should
be considered when refractory SE is being treated.
Recommendations:
Class
A:
In the treatment of seizures and SE, both the use of diazepam
followed by a phenytoin or the use of lorazepam are acceptable acute
treatment strategies, although lorazepam may be more effective in
terminating SE.
Class
B:
In
pediatric SE patients, IV lorazepam should be utilized rather than
IV diazepam because of the greater risk of respiratory complications
with IV diazepam use.
Phenobarbital
is an effective alternative to the use of phenytoin in SE.
Class
C:
High
dose phenytoin (up to 30 mg/kg) may be more effective in treating
SE than standard doses.
Because
it is water-soluble, fosphenytoin may be useful when safety concerns
with the use of phenytoin exist.
The
rapid infusion of IV valproate may be considered after benzodiazepines
and phenytoins in the treatment of SE, or when hypotension is a potential
concern.
IV
propofol may be considered when other drugs such as high-dose barbiturates
are being considered in the treatment of refractory SE.
Comments:
Most
of the recommendations that can be made regarding the treatment of
SE in the ED are unfortunately Class C, since few randomized controlled
trials have been conducted to support higher class recommendations.
Because of the great deal of resources necessary to conduct
a prehospital or ED study of SE, including the use of an exception
to informed consent, it is not likely that higher level recommendations
will be made based on new ED data.
At best, a greater number of Class B recommendations may be
made in the future as a result of publications of case series in the
Neurology or Emergency Medicine literature.
Case Management and Outcome
The patient is initially treated with four doses of
IV lorazepam, to a total dose of 8 mg, which is approximately 0.1
mg/kg. However, the patient
continues to seize. The
airway is patent with adequate vital signs and pulse oximetry readings. The patient is then given a rapid infusion of one gram of fosphenytoin
over 10 minutes, and then receives a second infusion of 500 mg of
fosphenytion over five minutes.
The generalized seizure then stops.
The patient is stable but remains unresponsive for over 30
minutes in the ED while an ICU bed is being obtained.
Cardiopulmonary, metabolic and toxicology tests are
negative, as is a non-infused CT of the head.
The initial levels of both phenytoin and phenobarbital were
found to be sub-therapeutic.
An EEG is arranged for and is completed upon arrival to the
ICU, within about 120 minutes of the seizure onset in the ED.
The patient is consulted by a neurologist, and is found not
to be in subtle status epilepticus based on the EEG result and neurologic
exam. The patient awoke
completely within 12 hours and was discharged from the ICU the next
day without any morbidity related to this prolonged seizure.
The patient was discharged home two days later with the instructions
to take his medications as prescribed, with neurology follow-up one
week later.
Diagnoses:
1. Generalized convulsive status epilepticus due to AED non-compliance
and sub-therapeutic drug levels.
2.
Post-traumatic seizure disorder.