Convulsive status epilepticus (SE) is often associated with poor outcome. This section presents the etiology, related electrophysiology, course and consequences of convulsive SE.

Important clinical lessons about the effects and prognosis of convulsive SE have emerged from studies:

• Some damage appears to accrue from the epileptic neural activity itself, although systemic factors such as hypotension, hypoxia, and acidosis may add to the neurologic complications.
• The longer the duration of SE, the more refractory it becomes and the more neuronal damage occurs.
• Clinical and experimental data suggest that 30 minutes of convulsive SE is a critical duration in neurologic function and probably in prognosis. This figure is far less certain for other forms of SE, particularly nonconvulsive forms.

Complications

Generalized convulsive status epilepticus (GCSE) is the most dramatic, most dangerous, and best-studied type of SE. It is potentially life-threatening but also treatable. A plan for medical management and pharmacotherapy is crucial. The clinician needs to understand its etiology, electrophysiology, pathophysiology, course, and consequences.

Symptoms

Convulsive SE is readily recognizable. It may start with simple or complex partial seizures but often begins with a generalized convulsion. Convulsions recur, most lasting only a minute or so, along with intervals of persistent unresponsiveness. Each convulsion may begin with several seconds of a tonic phase with tensing of extensor muscles and forced expiration, followed by a clonic phase with gradually slowing clonic movements. Both phases usually involve bilateral and symmetric movements, although there may be a focal onset with head or eye deviation, even without unilateral limb movement. Consciousness is impaired, at least from the time of tonic seizures.

Less often, convulsions are continuous. In this case clonic movements eventually diminish, often being replaced by repetitive jerking movements of the eyes, eyelids, or facial muscles alone or sometimes with intermittent limb jerking. These signs constitute "subtle" SE and imply continuing epileptic brain activity with a "decoupling" of electrical and motor systems.

Incidence

The incidence of convulsive SE is usually estimated to be about 60,000 cases each year in the United States (probably over half of them in children), but population-based surveys suggest that it may occur several times as often. The incidence of other forms of SE is less well documented.

Etiology and epidemiology

Convulsive SE is not a disease itself but, rather, a serious manifestation of some underlying disorder. The following list shows etiologies and percentages of patients affected; these figures are obtained from a summary of several studies of adult patients.

These percentages total more than 100% because of multiple causes. For instance, a patient with a congenital lesion and chronic epilepsy may experience anticonvulsant withdrawal or infection.

The causes of convulsive SE may vary tremendously in different populations. In urban hospitals, for example, SE is more often related to alcohol and drugs. The causes or precipitants of convulsive SE are also different in patients with known epilepsy than in those presenting with acute, new illness. Congenital abnormalities and infection increase in importance in children.

Often, there is an interaction between acute systemic illness and earlier neurologic disease, including epilepsy and other earlier neurologic insults. A history of epilepsy is often assumed, but in actuality about two-thirds of SE cases occur in patients who have not had prior seizures.

About 1% of patients with epilepsy will have an episode of SE in a given year. Anticonvulsant withdrawal is often assumed in patients with epilepsy, although this may be less frequent than presumed. Anticonvulsant changes initiated by physicians may cause withdrawal seizures as often as patient noncompliance. Adding new anticonvulsants may alter metabolism and lead to subtherapeutic or toxic levels of prior medications.

Infections may have a role in epileptogenicity, but several antibiotics also can precipitate seizures and alter anticonvulsant metabolism.

The epidemiology of convulsive SE has several clinical implications:

• Convulsive SE usually has an identifiable cause. Look for it. Trauma, new or prior vascular disease, metabolic derangements, drug toxicity (due to prescribed or "recreational" drugs), and infection not only help to explain the SE but often determine the subsequent course; they must be found to be treated appropriately. Alcohol abuse and benzodiazepine withdrawal are common contributors.
• There is often more than one cause or precipitant: medication withdrawal, infection, or sleep deprivation may add to an earlier illness and precipitate convulsive SE. In some series, up to 50% of patients have either an infection or a recent medication change. Conversely, even in acute illness, convulsive SE occurs more often in people with prior neurologic deficits.
• Convulsive SE can be the first sign of neurologic disease, especially in children, in whom up to 10% of initial seizures (particularly febrile seizures) may be SE.

Convulsive status epilepticus (SE) is rarely difficult to diagnose. Other forms of SE, however, may be mistaken for altered mental status from other causes, or for movement disorders. These other forms include both generalized seizures and partial or focal seizures.

The management of other forms of SE is often similar, though less urgent, than the management of convulsive SE.

Absence (petit mal) SE

Absence SE implies generalized epileptiform EEG discharges. Synonymous (and somewhat confusing) terms include "spike wave stupor" and "epileptic twilight states."

Because of the difficulty of detection, it is hard to know how often absence SE occurs. It may occur one-fourth as often as convulsive SE. Three different syndromes have been described:

• Classic absence SE typically occurs in younger patients with absence epilepsy. Very frequent classic absences or (less frequently) continuous absence is noted.



• Atypical absence SE occurs in children with symptomatic generalized epilepsy (e.g., the Lennox-Gastaut Syndrome). There is decline of mental status associated with significantly increased persistence of generalized slow spike wave. Diagnosis may be difficult because cognitive status is often impaired at baseline in this population and generalized slow spike wave is quite common in the baseline EEG as well.



• Absence SE of late onset occurs in a variety of circumstances. Some patients may have had previous symptomatic epilepsy but have been seizure-free and off medications for years. In other older patients, absence SE is the first presentation of epilepsy. It may be precipitated by medications such as Cipro or baclofen, or may occur following generalized convulsions or electroconvulsive therapy. Misdiagnosis is common unless there is a high level of suspicion; decreased mental status is often attributed to psychiatric or other systemic illnesses.

Onset may be sudden or gradual. Patients may be awake, walking and talking, although they are often confused. Motor activity may be preserved but clumsy. There is occasionally some blinking or myoclonus.

Absence SE can persist for days or weeks without being recognized. A history of epilepsy is suggestive. Most cases may be missed, but EEG can readily confirm the diagnosis. Some EEGs show generalized 3-Hz epileptiform discharges. Some may be secondarily generalized from a focus.

EEG of a 33-year-old woman with a history of epilepsy, now ambulatory and speaking, but confused at the time of office visit; approximately 3-HZ generalized spike-and-slow wave discharges with a frontal and central emphasis.

Especially in younger patients with primary generalized epilepsies, benzodiazepine therapy is often rapidly successful. Valproic acid may be better at preventing recurrences. Most patients return to normal, although recurrence of absence SE is relatively common. In older patients and those whose SE has a less certain cause, the response to anticonvulsant therapy can be delayed.

The typical absence status of patients with prior epilepsy is not thought to be life-threatening, but occasionally episodes end with a generalized convulsion. Absence SE is probably the most benign type of SE in terms of potential neuropathophysiologic consequences and may warrant less aggressive treatment than other forms of SE. For example, treatment with anesthetic drips is usually not pursued in this situation.

Myoclonic status epilepticus

Myoclonic status epilepticus (MSE) also occurs in several forms. The most severe form, which is highly associated with the eventual death of the patient, occurs after anoxia. Persistent myoclonus due to a severe encephalopathy without MSE is potentially reversible. The EEG helps determine whether myoclonus is the sporadic sign of an encephalopathy (with a better prognosis) or part of MSE. After anoxia, MSE is better considered a sign of a severely damaged brain than a treatable epileptic condition. MSE may have motor manifestations limited to "subtle" status, also an ominous sign after anoxia.

Less severe forms of MSE occur as a manifestation of generalized epilepsies such as juvenile myoclonic epilepsy. This form of MSE may include prolonged epileptic myoclonus without loss of consciousness. The EEG shows very characteristic generalized polyspike and slow wave discharges with a normal background between episodes. Episodes may go on for hours (with preserved consciousness), but the prognosis is excellent given the prior normal neurologic function.

Patients can also return to baseline in the MSE of progressive myoclonus epilepsies, although the epilepsy may be part of a progressive debilitating disease.

In all these conditions, the EEG can help distinguish MSE from encephalopathies with less rhythmic abnormalities.

Tonic or clonic SE

Tonic SE is rare. It is seen primarily in children, particularly those with Lennox-Gastaut syndrome. This form of SE does not respond well to medications, as is true of most seizure types in Lennox-Gastaut syndrome. Rarely, benzodiazepines have been cited as triggering tonic status. Tonic (and atonic) SE is distinctly uncommon in adults, especially those with normal interictal neurologic function.

Generalized clonic SE is also a pediatric condition. Clonus is often of low amplitude. Both sides of the body are usually involved but may move asynchronously.

Complex partial SE

Complex partial status epilepticus (CPSE) implies impairment of consciousness due to seizures with a focal cortical origin. The disorder is sometimes called fugue state or psychomotor status.

Confusion is the most common symptom. A sudden alteration in behavior, particularly in a patient with prior epilepsy, should suggest the possible diagnosis of CPSE. A diagnosis of CPSE is frequently invoked to explain bizarre behavior, but this type of SE is actually uncommon. Some patients may have complex partial seizures with a prolonged postictal phase. CPSE may be continuous or include frequent discrete seizures without recovery between them; the latter series of spells account for some of the prolonged episodes.

CPSE can go on for weeks or even months, and patients may have prolonged cognitive deficits after CPSE. It can be very difficult to distinguish from absence SE. Patients with CPSE may exhibit more bizarre behavior during seizures, so the disorder also is confused with psychiatric disease or metabolic encephalopathies with delirium.

The usual site of origin is assumed to be mesial temporal structures with limbic connections, but recordings obtained from implanted electrodes have shown that frontal lobe onset is common. The EEG may show the seizure clearly (but this is less likely in frontal areas without implanted electrodes) or may show just persistent focal slowing. Seizures may spread rapidly, and nonconvulsive SE with generalized discharges ("absence SE") may actually arise from a focus.

Increasing reports of cognitive and other sequelae following prolonged CPSE have lent a greater urgency to its interruption, but treatment is usually not as aggressive as for generalized convulsive SE. Most CPSE responds relatively rapidly to anticonvulsants but may recur frequently and even regularly in the same patient, even with adequate anticonvulsant therapy.

Simple partial SE (epilepsia partialis continua)

Epilepsia partialis continua (EPC) usually refers to partial motor status. Continuous unilateral facial or hand clonic jerking are most commonly observed, but any group of muscles can be involved. An acute structural lesion must be considered and ruled out, but lesions are not always found even with contemporary imaging. Consciousness may be impaired because of secondary effects of the structural lesion. The EEG often demonstrates periodic lateralizing epileptiform discharges (PLEDs) in a corresponding distribution.

As in all other areas of medicine, effective treatment of status epilepticus (SE) is facilitated tremendously by the correct diagnosis! Convulsive SE is rarely a diagnostic difficulty, but nonconvulsive forms, including episodes after generalized seizures, may be difficult to recognize or missed altogether.

Differential diagnosis

Almost all published protocols and guidelines refer to generalized convulsive SE (GCSE). Generalized nonconvulsive SE (NCSE) after convulsions should probably be considered as much of an emergency as GCSE. Other forms of SE are of less certain morbidity and urgency. Medication use is generally similar, if less immediate. Nevertheless, the pathophysiologic underpinnings of many different types of SE (with the possible exception of absence SE, EPC, and myoclonic status after anoxia) argue for urgent treatment in almost all cases. Other forms of SE can lead to convulsions, and a casual approach is inappropriate.

Phenytoin and now fosphenytoin are probably the most frequently used anticonvulsants for SE. The older formulation (phenytoin in a basic solution including ethylene glycol) is still used because its cost is substantially lower. However, intravenous phenytoin has three major disadvantages:

• A longer time is required to achieve therapeutic levels.
• Intramuscular administration is not possible.
• Significant soft tissue damage may occur with extravasation.

The newer formulation (fosphenytoin, a phenytoin prodrug) can be administered more quickly, an important advantage when seizures must be controlled quickly. Because a basic solution is not required for dissolving fosphenytoin, intramuscular administration is safe and extravasation carries little risk.

Cardiac rhythm abnormalities and hypotension can occur with both formulations.

Both phenytoin and fosphenytoin cause minimal sedation. This advantage over other anticonvulsants is probably overstated but it may be pertinent for patients with head trauma, hemorrhage, or raised intracranial pressure, for whom it is important to monitor alertness. Patients with GCSE are unconscious, and the most immediate concern is stopping the seizures.

In the absence of acute structural lesions, both phenytoin and fosphenytoin may be successful alone in up to 80% of patients with GCSE. If either is used, oral phenytoin can then become a long-term maintenance medication. This obviates the necessity of changing or adding drugs.

Patients may need adjunctive benzodiazepines to interrupt convulsions if they occur during phenytoin infusion. The VA Cooperative Study, for instance, found that phenytoin with diazepam stopped GCSE more quickly than phenytoin alone. Many authorities recommend phenytoin as the primary treatment of GCSE, sometimes after initial interruption of convulsions with a benzodiazepine.

A usual loading dose for phenytoin is 15 mg/kg, but 20 mg/kg is reasonable before concluding that phenytoin is insufficient. It should be given by intravenous bolus or in saline solution at a maximum rate of 50 mg/min. (It may precipitate in glucose solutions.) Intramuscular phenytoin is poorly absorbed and should not be used.

The usual loading dose for fosphenytoin is 15-20 mg phenytoin equivalent (PE)/kg. It can be administered as quickly as 150 mg PE/min and there are theoretical advantages to doing so. Rapid rates are associated with greater risk of cardiac toxicity with both formulations, however. Intramuscular fosphenytoin is safe and readily absorbed; a "loading dose" typically leads to therapeutic levels within half an hour.

Conduction defects are the primary cardiac toxicity, but hypotension is not rare. Cardiac monitoring is appropriate during phenytoin infusion. Elderly patients or those with cardiac disease may not tolerate phenytoin as well as phenobarbital. Acute toxicity is more closely related to the infusion rate than to total dose. Patients with possible complications may tolerate greater doses in slower infusions.

The recently available intravenous formulation of valproic acid has several advantages:

• It is not sedating
• Hypotension and respiratory comprise are not issues
• It can be administered relatively quickly

It has not been compared directly to phenytoin, fosphenytoin, or phenobarbital, however, and may not be as effective in GCSE.

Valproic acid is administered in a loading dose of 25 mg/kg. Higher doses are occasionally used. The package insert recommends an infusion rate of no faster than 20 mg/min, but several reports have documented that infusion rates between 100 and 150 mg/min are safe and well tolerated.

Valproic acid may significantly increase phenobarbital levels or free phenytoin levels if these medications have already been administered.

Caution should be exercised if the patient is being treated with lamotrigine (Lamictal, a widely used maintenance anticonvulsant) because administration of valproate may quickly double lamotrigine levels. It is prudent to hold lamotrigine doses in this situation and check serum levels within 24 hours.

Rectally administered valproic acid syrup is absorbed irregularly and is rarely used now that an intravenous formulation is widely available. It can be useful if intravenous access can not be obtained, however, because it is absorbed more rapidly than valproic acid given by mouth and bypasses the hepatic first-pass effect. The usual dose is 25 mg/kg or higher. Valproic acid syrup is cathartic. It should be mixed in equal volumes of water prior to administration.

Phenobarbital is often used if phenytoin is insufficient, but it is frequently avoided out of fear it will cause sedation or respiratory compromise (especially after several doses of benzodiazepines). One of its advantages is a relative lack of cardiac toxicity until very high doses are reached.

Phenobarbital has been compared favorably with a combination of diazepam and phenytoin; in the VA Cooperative Trial, clinical response was actually faster with phenobarbital. Respiratory depression and hypotension are likely if phenobarbital, a barbiturate, is used together with benzodiazepines.

Loading with up to 20 mg/kg is reasonable. It may be administered as quickly as 100 mg per minute in normal-size adults if respirations are carefully monitored. Loading is faster than with phenytoin, but its lipid solubility is lower and brain penetration is slower. Nevertheless, phenobarbital may act quickly, even before therapeutic levels are established.

Some SE may be refractory to phenytoin, but high enough doses of phenobarbital will control almost all seizures. Very high doses require artificial ventilation and may cause hypotension, but they may be tolerated better than expected. Sedation must be expected with high doses, but levels below 40 mcg/mL should not produce prolonged coma.

Diazepam (Valium, Diastat) is a very common first treatment for SE, but conservative management would restrict it to patients with continuing convulsions or those having another convulsion during infusion of a maintenance medication. Reported efficacy rates in SE have varied widely, from 38% to 83%. Diazepam can interrupt convulsive SE rapidly but should not be used alone.

The usual practice is to administer 10 mg (0.15 mg/kg) intravenously over a few minutes, repeating if necessary. Rectal administration has been effective, particularly in children, and a gel suitable for rectal administration (Diastat) is available. Doses of the rectal gel necessary to terminate seizures are somewhat higher and vary by weight and age. A buccal formulation (Diazapam Intensol) is less well studied but widely considered effective as well. Both rectal and buccal formulations bypass first-pass hepatic metabolism and thus result in reasonable levels within about 30 minutes. In contrast, both intramuscular and oral diazepam are absorbed slowly and should not be used when acute seizure control is necessary.

Diazepam is very lipid-soluble, enters the brain rapidly, and may have an anticonvulsant effect within a minute after intravenous administration. Nevertheless, it redistributes to many tissues and its CNS effect declines in 20 to 30 minutes, so longer-acting anticonvulsants should be used concomitantly to prevent recurrent seizures or SE. Repeated doses may lose effectiveness but produce metabolites with prolonged elimination half-lives and potential toxicity, including prolonged coma.

Continuous infusion of diazepam (generally 4 to 8 mg/h) is often discussed for the management of SE but is rarely practiced, probably because the optimal doses have not been clearly established and rapid acute tolerance may develop. Continuous infusion should be used in intensive care units only. Iatrogenic apnea (often ascribed to seizures or to "tongue swallowing") can occur suddenly.

Lorazepam (Ativan) has several advantages:

• It acts rapidly enough to interrupt seizures quickly.
• It also has a more prolonged anticonvulsant effect. (Some physicians consider it to satisfy the requirements for both the acute interruption of SE and prolonged protection against recurrence.)
• Compared to diazepam, doses are approximately half as large and it is half as lipid-soluble. Its brain penetration is slower but still rapid.
• Its effect declines less rapidly than diazepam.
• It has no active, troublesome metabolites.

Many epileptologists prefer lorazepam because of its favorable pharmacokinetics, but direct comparative studies are few. A double-blind, randomized trial found lorazepam marginally more effective than diazepam in controlling SE, with an onset of action not significantly different. Adverse effects are similar to those of diazepam, although perhaps less sudden. Lorazepam may provide 12 hours of anticonvulsant effect, but acute tolerance may reduce its maintenance value.

Midazolam (Versed) is used both acutely to treat SE at presentation and as a continuous anesthetic drip after SE has proven refractory to standard treatment (see below). Acutely, it may be given in intravenous boluses of 0.2 mg/kg (5 to 20 mg). Onset of therapeutic effect is extremely rapid because of high lipid solubility, but its effect is short-lived, and relapses of seizures may be expected. The very short duration of action allows clinical assessment soon after its discontinuation.

Midazolam may be the best intramuscular treatment of SE when this is the only available route.

Clonazepam (Klonopin) appears similar to other benzodiazepines and is popular in Europe, but it is not available in intravenous form in the United States for the treatment of SE.

When a benzodiazepine and one or more longer-acting anticonvulsants have not terminated SE, strong consideration should be given to treatment with continuous intravenous or inhalational anesthesia. This always requires intubation, respiratory support, and treatments to maintain normal blood pressure. Continuous EEG monitoring is mandatory in this situation.

The goal is escalation of anesthetic medications until seizures are controlled or side effects (usually hypotension) preclude further dose increases. Many have suggested that if SE has been difficult to control, anesthetic medications should be increased until a "burst suppression" or flat record is achieved. This state is then maintained for at least 24 hours and the anesthetic medications are gradually tapered. Maintenance anticonvulsant medications are administered in the interim (usually by nasogastric tube) in the hope that these will prevent recurrence of seizures as the anesthetic medications are tapered.

Because three longer-acting anticonvulsants are now available in intravenous form, it is tempting to try all three before moving on to intubation and anesthetic treatment. In GCSE, this may be the wrong thing to do. In the VA Cooperative Study, only 7% of patients failing the first treatment responded to the second and only 2% of those failing two treatments responded to a third. A strong argument can therefore be made for proceeding to continuous anesthetic treatment within a half-hour of onset of GCSE.

Midazolam

Midazolam, which can be used for acute treatment at presentation (above), can also be used as a continuous anesthetic treatment for refractory SE. A loading dose of 0.2 mg/kg is typically administered, followed by a drip of 0.2 to 2 mg/kg per hour. Achieving burst suppression or isoelectric EEG typically requires escalation towards the higher doses. Hypotension appears less problematic than with the other anesthetics discussed. Tachyphylaxis may occur after 48 hours and require further escalation of doses.

The very short half life allows rapid assessment of mental status after the drip is tapered and terminated, a decided advantage over pentobarbital. The more rapid recovery may also shorten time intubated or in the ICU. Cost was a concern until the generic intravenous formulation became available.

Propofol

A 2mg/kg loading dose is typically administered followed by a 5 to 10 mg/kg per hour drip. Hypotension can occur. The high lipid content of the formulation is a concern, especially in patients with significant hyperlipidemia or atherosclerosis. Involuntary myoclonic movements have been reported at induction during routine surgeries but their meaning is uncertain and we have not encountered them in the treatment of SE. The medication is very lipid-soluble and has a short half life, allowing a more rapid recovery after tapering than with pentobarbital.

Pentobarbital

Loading doses of 3 to 5 mg/kg followed by infusion of 1 to 4 mg/kg per hour are typical.
Effectiveness is assessed by effect on the EEG, with an attempt to eliminate seizures or aim for burst suppression. (Most authors seek a burst suppression pattern.) Blood levels are more useful for indicating residual toxicity than for assessing therapeutic effect.

The half-life of pentobarbital is approximately 20 hours (shorter than for phenobarbital, so it dissipates sooner), but it may be extended at higher levels. Pentobarbital accumulates in fatty tissues other than brain with prolonged treatment and these stores must be mobilized and secreted after administration ceases. One should therefore not attribute prolonged coma after pentobarbital treatment to a "burnt-out" brain before the medication has had time to dissipate.

All SE should be suppressible with adequate pentobarbital doses, but hypotension is common. Usually, volume replacement and low doses of vasopressors are sufficient. Myocardial function and temperature regulation can be impaired. Most reports of pentobarbital use show a very high mortality, usually attributed to severe underlying diseases causing SE refractory enough to require pentobarbital.

An advantage of pentobarbital, besides its invariable effectiveness when used in large enough doses, is that it reduces cerebral metabolism and blood flow. The infusion is also easy to adjust. The optimal duration of barbiturate-induced coma has not been established; recommendations range from 4 to 72 hours. Probably pentobarbital should not be withdrawn until the patient has a therapeutic blood level of two other anticonvulsants.

Inhaled anesthetics

Inhaled anesthetics are less well studied and far less convenient than the drugs already described but may be useful for patients who are allergic to pentobarbital. Most inhaled anesthetics increase cerebral blood flow, a theoretical disadvantage. This problem probably applies least to isoflurane, possibly the most effective anesthetic with the least cardiovascular effect in the setting of SE. Halothane is used relatively frequently, but isoflurane may produce a burst suppression EEG tracing with less severe cardiovascular morbidity. Vasopressors may be needed with both agents. Nitrous oxide does not appear effective. Enflurane can precipitate convulsions.

Other agents

Neuromuscular blocking agents eliminate motor activity, but they are not anticonvulsants. They may provide false reassurance when SE continues on an electrical and metabolic basis. They can help when excessive movement impairs oxygenation, acid-base balance, or temperature regulation, but adequate doses of anticonvulsants, particularly pentobarbital, will obviate these problems.

Steroids and osmotic agents may be used to treat cerebral edema that results from prolonged SE, particularly in children, but their efficacy has not been established.

Rarely, a persistent seizure focus causing refractory partial SE may be resected surgically.

Most medication trials have studied patients with GCSE. The same medications may treat other forms of SE. Intravenous benzodiazepines usually interrupt absence SE, and subsequent treatment may be unnecessary. For patients with continuous generalized discharges and coma, however, intravenous benzodiazepines are often insufficient.

For partial or nonconvulsive SE, enteral valproate and carbamazepine are more valuable, although the response may take days; rarely will pentobarbital or anesthetics be necessary. In children, phenobarbital is often preferred to phenytoin because of better absorption, greater efficacy, and possibly fewer long-term side effects.

When SE does not respond to treatment as expected, the clinician's attention should refocus along several lines:

• Is the diagnosis of SE correct?
• Has the underlying cause been correctly assessed? This is crucial, because SE is most likely to continue when trauma, hemorrhage, or infections such as encephalitis remain untreated.
• Have medications been given in adequate doses? (The 1000-mg standard phenytoin infusion may be insufficient, for example.)
• Have medications been adequately absorbed? Absorption can be a problem if there are difficulties with intravenous access or if the drug is given by another route.
• Has the SE recurred after successful treatment? This situation most often results from inadequate attention to maintenance levels of longer-acting anticonvulsants or lack of treatment of the underlying disease.

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