 Lesson 14, Volume 16—Management of Seizures in the Critical
Care Unit
By Shahram Khoshbin, MD
Effective December 31, 2004, PCCU Volume 16 is available for review purposes only. CME credit for this volume is no longer being offered. Objectives
- To distinguish seizures from nonseizure events in the CCU patient.
- To identify seizures by classification (focal vs generalized).
- To identify new seizures due to CNS lesions.
- To identify seizures provoked by metabolic or drug effects.
- To approach the management of repeated seizures and status
epilepticus.
Key words
nonconvulsive status epilepticus; nonseizure paroxysmal
events; seizure risk in critical care unit; seizure treatment;
seizures; status epilepticus
Abbreviations
CCU = critical care unit; CPS = complex partial
seizure; SPS = simple partial seizure
Although seizures are common
phenomena with a prevalence of 6.0 per thousand,1 they
constitute a major neurologic symptom indicating serious underlying
etiology. Seizures occurring in the critical care unit (CCU) are
of particular concern and involve a number of issues. When neurologists
are called in to consult in the CCU, the first issue that arises
is whether the observed event that precipitated the consultation
was a seizure. As a rule, physicians do not observe the event.
The nursing and support staff are very good in depicting the paroxysmal
symptoms. However, frequently, nonseizure phenomena are reported
as a seizure. Proper identification becomes crucial because it
is important to diagnose seizures early, and it is also important
not to treat just any event with anticonvulsant therapy. Furthermore,
the type of seizure (generalized vs focal) will dictate both evaluation
and management.
In general, seizures may occur in four settings:
(1) in a patient with a known seizure disorder admitted to the
CCU because of refractory seizures or other etiologies resulting
in worsening of the seizures; (2) in patients with known CNS lesions,
such as tumors, previous strokes, or congenital lesions, but no
history of seizures, who have a reduction in seizure threshold;
(3) new seizure in a patient with no known neurologic lesions;
and (4) special situations such as patients who are immune-suppressed
or postoperative, or have sustained multiple traumatic injuries
or burns. However, a majority of seizures are provoked, occurring
in the context of metabolic-hypoxic encephalopathy or as a result
of drug withdrawal or drug toxicity.
The Differential Diagnosis of Seizures in the
CCU
The international classification of epileptic seizures2 offers
a rational approach to evaluating seizures and differentiating
seizures from nonseizure events. Seizures are divided into partial
(focal) and generalized (convulsive or nonconvulsive).
The term focal seizure implies that the symptom
derives from activation of a circumscribed neuronal system in one
or the other hemisphere. Focal seizures usually do not impair consciousness
and are referred to as simple partial seizures (SPSs). Focal seizures
that start either with an impairment, but not loss, of consciousness
or after an SPS are referred to as complex partial seizures (CPSs).
Both SPSs and CPSs can evolve into generalized tonic-clonic convulsions
or nonconvulsive repetitive seizures.
Diagnosis of generalized tonic-clonic convulsions
and frequent repeated seizures with no recovery of consciousness
between seizures—referred to as status epilepticus—is
usually easy. Nonconvulsive seizures, SPSs, and CPSs present a
challenge for diagnosis because they are frequently mistaken for
movement disorders, confusional episodes, and other causes of loss
of consciousness (of the generalized seizures petit mal is usually
not seen in the adult population). The following differential diagnoses
should be considered:
- A motor event may be associated with movement disorders,
particularly, myoclonus, but also polymyoclonus, startle response,
or dystonia; with posturing, such as decerebrate or decorticate
posturing in patients with increased intracranial pressure, or
clonus (hyperreflexia or myokymia); or with benign, simple phenomena
such as shivering, tremor, sleep disorders (restless leg syndrome),
agitation, and reaction to hallucinations.
- Causes of loss of consciousness, usually syncope, include
vasovagal attack, orthostatic hypotension, valvular cardiac disease,
and arrhythmias. All these events may include brief convulsive
movements without the development of a seizure.
- Episodic changes in consciousness and episodic confusion are
usually a result of toxic metabolic encephalopathy.
- Psychiatric issues, such as ICU psychosis, panic attacks,
pseudoseizures, hyperventilation, and conversion disorder, can
be seen concomitantly with serious medical illness.
Certain clinical signs can be helpful in differentiating
seizures from these nonseizure events. In general, movements that
can be modified by positioning the limbs are not seizures. The
presence of rhythmic eye movements and eye deviations, intermittent
pupillary changes (hippus), and adversion (turning of the head)
are clues that point to a seizure phenomenon. Alternating right-left
body movements and hip movements are usually not seen with epileptic
seizures. The EEG can be helpful, especially if the event is captured
during the recording. However, in metabolic encephalopathies, certain
EEG patterns (triphasic potentials) can be difficult to distinguish
from repeated discharges. Experienced electroencephalographers
should interpret EEGs in the CCU.
Seizures Associated With Neurologic Lesions
As a rule, when seizures result from reduced seizure
threshold in a patient with a known CNS lesion, or in a patient
who has acquired a CNS lesion after hospitalization, the seizure
will be focal. Certain groups of patients are particularly susceptible
to developing new CNS lesions: patients who are postoperative,
particularly after cardiac valvular surgery; patients with multisystem
trauma; patients with burns; patients who are immunosuppressed;
and patients who have experienced cardiopulmonary arrest. Stroke
is a common etiology for older patients. Seizures are particularly
common with hemorrhagic events including intracerebral hemorrhage
and subarachnoid hemorrhage.3 Ischemic stroke may also
be present with seizures; however, seizure is not a common presentation
of stroke. Seizures occur in roughly 10% of patients with ischemic
stroke, mostly in embolic stroke. The likelihood increases with
patient age.
Patients with brain tumors frequently present with
seizures. However, these patients are usually taking anticonvulsant
drugs, and if seizures occur in the context of the CCU, they are
usually due to inadequate antiepileptic drug levels.
In patients who have sustained head trauma with loss
of consciousness, there is risk of a seizure after admission to
the CCU. If the loss of consciousness is brief, the risk of seizure
is lower. However, in patients with severe head injuries, the risk
may be as high as 10%, and in children, up to 30%. The sooner the
seizure occurs after the trauma, the less likely late seizures
will develop.4 One issue of controversy is the use of
prophylactic antiepileptic drugs in patients with head injury.
Different studies have reported a decrease in the incidence of
seizures with the use of phenytoin; however, in general, the medication
should be discontinued if no seizures occur and the EEG findings
are negative.
CNS infections are common causes of seizures in the
CCU. Bacterial meningitis, bacterial abcesses, and viral encephalitis
can present with seizures. Patients with herpes encephalitis frequently
present with partial complex seizures because of the disorder’s
predilection for creating focal hemorrhagic lesions in the temporal
lobe.
In patients who are immunosuppressed or have connective
tissue disorders, seizures indicate a major neurologic complication.
For instance, in patients with AIDS, cryptococcal meningitis, toxoplasmosis,
or CNS lymphoma is usually the reason for a new seizure. Immunosuppressant
drug toxicity also may be a reason for seizures. For example, cyclosporine
toxicity is a common cause of seizures in this patient group. Thus,
it is necessary to include a lumbar puncture as part of the initial
evaluation in a patient with seizures, particularly if the seizures
have a focal signature or there is concomitant fever.
Seizures Provoked by Metabolic Abnormalities
As a rule, seizures provoked by metabolic abnormalities
are generalized. Metabolic etiologies, particularly electrolyte
disturbances such as hyponatremia, hypocalcemia, and hypoglycemia,
are common causes of seizures. Both the serum levels and the rate
of development of the electrolyte imbalance are important in seizure
development. In patients who are postoperative, hyponatremia is
of particular concern. It may be due to hypervolemic dilutional
reduction in sodium because of excessive fluid loading. Inappropriate
antidiuretic hormone also may develop in these patients.
Seizures can be seen in patients with hyperglycemia
as well as hypoglycemia. In hyperglycemia, seizures are usually
focal, while seizures are usually generalized in hypoglycemia.
Hypomagnesemia is a rare cause of seizures. Although hypercalcemia
is frequent among patients in the CCU, seizures are not associated
with increased calcium. Hypocalcemia is not a very common occurrence
in the CCU, but seizures are common in hypocalcemia.
The best way to evaluate metabolic encephalopathy
is through EEG monitoring. Electrolyte disturbances, renal failure,
and hepatic failure causing metabolic encephalopathy all cause
major changes in the EEG. Usually, bilateral slow activity is noted,
in contradistinction to focal findings of CNS lesions.
Certain conditions deserve special attention. For
example, in patients who are pregnant, preeclampsia is a risk factor
for development of seizures. This usually occurs in the third trimester,
but also has been seen earlier in the second trimester or postpartum.
In women who are pregnant, there is also the additional risk of
venous thrombosis, which usually presents with seizures.
Seizures Provoked by Drug Toxicity or Withdrawal
Drugs probably are the most common sources of seizures
in the CCU. Both toxicity of and withdrawal from certain drugs
may be seen. Secondary metabolic derangements, such as renal failure,
also compound the problem.
Drug withdrawal is of particular concern in patients
who are receiving narcotics for the treatment of pain. Usually,
after a few days of parenteral or intramuscular administration
followed by an abrupt withdrawal, patients develop seizures from
morphine or meperidine withdrawal. Withdrawal from benzodiazepines
may also cause seizures. One very interesting complication of this
type of withdrawal is the development of nonconvulsive status epilepticus.
These patients usually exhibit prolonged suppressed consciousness
at times with minor oral-buccal automatic behavior and/or myoclonic
discharges.
The best-known cause of withdrawal seizure is alcohol
withdrawal. Alcohol withdrawal is not only a common etiology of
seizures seen in the emergency room, but it is also one of the
causes of status epilepticus. In addition, seizures secondary to
head trauma, subarachnoid hemorrhage, and metabolic abnormalities
as the result of alcoholism may be seen. Alcohol-withdrawal seizures
are usually generalized, and they can occur as early as 8 to 10
h after withdrawal. Rarely, alcohol-withdrawal seizures can be
focal, and there is a high risk of developing delirium tremens
following seizures.5 Sometimes, alcohol-withdrawal seizures
occur in clusters.
Drug toxicity is also a known precipitant of seizures
in the CCU. However, to relate seizures to the effect of these
medications, toxic levels must be shown. Certain medications used
in the CCU are particularly known to cause seizures. These include
respiratory drugs such as aminophylline and theophylline; certain
antibiotics, particularly penicillin derivatives, ciprofloxacin,
isoniazid, and imipenem; immunosuppressioant drugs such as cyclosporin
and cyclophosphamide; antiarrhythmia drugs such as lidocaine; and
psychiatric drugs, particularly tricyclic antidepressants, clozapine,
and lithium.
Status Epilepticus
It is now the consensus that a seizure exceeding
5 min in length or the occurrence of three seizures in 1 h, or
continuous seizures for 30 min or lack of recovery between seizures
should be treated vigorously as status epilepticus. Status epilepticus
is usually convulsive, although seizures starting as an SPS or
CPS can evolve into convulsive status epilepticus. Most generalized
seizures terminate within 3 to 5 min. Seizures that last > 5
min or that follow one another with the patient unresponsive in
between can have serious neurologic and medical effects. During
the events, persistent contraction of muscles and derangements
of respiration occur.
The systemic complications may be just as deleterious.
Continuous contraction of muscles may lead to myglobinuria and
renal failure. Other systemic complications include (1) cardiovascular
complications, such as arrhythmias (both tachycardia and bradycardia);
(2) complications of hyperkalemia; and (3) the side effects of
anticonvulsant therapies. Respiratory suppression is also a side
effect of anticonvulsant therapy. Both respiratory and metabolic
acidosis, hyponatremia, hyperkalemia, and hypoglycemia may be seen.
Autonomic symptoms, particularly fever, excessive sweating, and
bronchial hypersecretion, are also complicating factors. Not only
does status epilepticus create damage due to the above complications,
but prolonged electrical discharge may also result in neuronal
damage, and therefore even nonconvulsive status epilepticus poses
risks associated with a seizure.
A certain group of patients are susceptible to status
epilepticus. Patients with seizures who have abruptly withdrawn
from their medication and and have concomitant drug or alcohol
abuse are more susceptible, as are patients who have experienced
acute stroke (either embolic or intracerebral hemorrhage) and those
with metabolic encephalopathy, hypoxic encephalopathy, CNS infections,
or head trauma. Status epilepticus can also be seen with secondary
hyperparathyroidism. On very rare occasions, absence status (petit
mal status) is seen in children. Repeated myoclonus may also
be an indication of what has been termed "status myoclonus." These
all require EEG evaluation and continued monitoring. On discharge
or transfer out of the CCU ?patient's ? usually placed on oral
anticonvulsants and reevaluated in 4-6 months.
Treatment of Status Epilepticus and Seizures in
the CCU
Because of the urgent nature of seizures, treatment
usually is started before evaluation has been completed. However,
correct diagnosis is crucial. Urgent evaluation may include (1)
careful review of drug history, (2) hematologic and serum analysis,
(3) neuroimaging, and (4) lumbar puncture. Although EEG is essential,
it usually is not obtained prior to onset of therapy. Stabilizing
the patient’s cardiorespiratory status should be the first
step. Drug therapy should start immediately if a seizure does not
stop within 5 min.
A number of medications are available. Parenteral
phenytoin was the first-line drug for many years. The availability
of the analog phosphenytoin, which offers less toxicity, makes
aggressive therapy less problematic. The use of benzodiazepines
is also fundamental. Diazepam was originally used; however, because
of its short half-life, repeated doses may be necessary. Lorazepam,
on the other hand, has a longer half-life and has become the drug
of choice. It is now recommended that once airway, blood pressure,
and cardiac rhythm have been stabilized, administration of phenytoin
or phosphenytoin should be started. Phenytoin is given in saline
at 50 mg/min, with continuous monitoring of EKG, for a total dose
of 15 to 20 mg/kg. Phosphenytoin is used in identical doses. However,
phosphenytoin can be given at a more rapid rate of up to 150 mg/min
and can be given in different IV solutions, including dextrose.
Diazepam and lorazepam are usually given in small doses, and usually
two or three consecutive doses of diazepam (5 mg) or lorazepam
(4 mg) is effective. Because of the risk of possible respiratory
depression, prophylactic intubation is usually performed.
Treatment of Persistent Status Epilepticus
If seizures do not respond to treatment with phosphenytoin
and lorazepam, phenobarbital is usually added. If recovery does
not occur within 30 to 40 min, other drugs should be added. These
include the barbiturate propofol,6 midazolam, and pentobarbital
to effect coma.7 At this level, continuous EEG monitoring
is desirable, and particularly with pentobarbital coma, a burst-suppression
pattern on the EEG directs the dosage and administration rate of
the medication. Pentobarbital coma may be needed for a few days
to a few weeks. Once convulsive seizures have been stopped, drugs
should be monitored by serum levels. However, in the CCU, anticonvulsant
levels can be ineffective because of protein binding and the presence
of hypoalbuminemia. False readings of drug serum levels may occur,
and patients may experience toxic levels of these drugs, particularly
phenytoin.8
References
- Annegers JF, Hauser WA, Lee RJ, et al. Incidence of acute symptomatic
seizures in Rochester, Minnesota, 1935–1984. Epilepsia 1995;
36:327–333
- Proposal for classification of epilepsies and epileptic syndromes:
Commission on Classification and Terminology of the International
League Against Epilepsy. Epilepsia 1985; 26:268–278
- Giroud M, Gras P, Fayolle H. Early seizures after acute stroke:
a study of 1,640 cases. Epilepsia 1994; 35:959–964
- Annegers JF, Grabow JD, Groover RV, et al. Seizures after head
trauma: a population study. Neurology 1980; 30:683–689
- Ng SKC, Hauser WA, Brust JCM, et al. Alcohol consumption and
withdrawal in new-onset seizures. N Engl J Med 1988; 319:666–673
- Stecker MM, Kramer TH, Raps EC, et al. Treatment of refractory
status epilepticus with propofol: clinical and pharmacokinetic
findings. Epilepsia 1998; 39:18–26
- Lowenstein DH, Aminoff MJ, Simon RP. Barbiturate anesthesia
in the treatment of status epilepticus. Neurology 1988; 38:395–400
- Cranford RE, Leppik IE, Patric B, et al. Intravenous phenytoin:
clinical and pharmacokinetic aspects. Neurology 1978; 28:874–880
Copyright ©2002 American College of Chest Physicians
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