Non convulsive status epilepticus Notes

Non-Convulsive Status

I. What every physician needs to know.

Status epilepticus (SE) is one of the most frequent neurological emergencies with an incidence of 20/100,000 per year and mortality between 3% and 40% depending on etiology, age, SE type and duration. SE has been defined as continuous seizure activity lasting more than 30 min, or two or more seizures in this duration without gaining consciousness between them. However, for clinical purposes, the “operational” definition has brought the time down to 5 minutes of continuous seizures or discrete seizures with incomplete recovery of consciousness. At least 65,000 cases of SE occur each year in the United States, demonstrating the importance of quick recognition and management.

SE falls into two categories: convulsive status versus non-convulsive status.The most life-threatening pattern, and that requiring the most urgent treatment, is convulsive status. Convulsive status epilepticus (CSE) can be further divided to generalized (generalized tonic-clonic, myoclonic, tonic, clonic) or partial (epilepsia partialis continua, hemiconvulsive). Non-convulsive Status Epilepticus (NCSE) can also be generalized (absence, generalized electrographic status epilepticus in coma), or partial (simple partial, complex partial, partial electrographic status epilepticus in coma). This chapter will only discuss NCSE.

Non-convulsive status epilepticus has been defined as a range of conditions in which electrographic seizure activity is prolonged and results in non-convulsive clinical symptoms. It is primarily a form of epileptic cerebral response which is dependent largely on the level of cerebral development and integrity, the presence or absence of encephalopathy, the type of epilepsy syndrome, the anatomical location of the epileptic activity. NCSE may be one of the most frequently missed diagnoses in patients with altered neurologic function. The missed diagnosis occurs in part because NCSE arises often in patients with other serious illnesses but also because the diagnosis may not be entertained due to its versatile presentation.

Both GCSE and NCSE should be considered a medical emergency and prompt diagnosis and treatment should not be delayed. The goal of any physician should be quick recognition of certain clinical conditions or situations where a high index of suspicion for NCSE should be retained. In any situation where a patient, especially an elderly person, presents with altered mental status, stupor or confusion, NCSE should be considered until proven otherwise. Furthermore, NCSE should be high on the differential in any patient with history of epilepsy/seizures with new evidence of medical or surgical stress. Finally, if witnessed seizure activity or convulsive SE has occurred and the patient has not returned to baseline despite apparently sufficient treatment, he or she must be treated as NCSE until EEG and/or clinical findings disprove this.

II. Diagnostic Confirmation: Are you sure your patient has Non-Convulsive Status?

For accurate diagnosis of NCSE, two factors should be evident. First, there needs to be an alteration in baseline cognition or behavior. Secondly, a concurrent epileptiform seizure pattern on EEG must be present.

Determining the etiology of the seizures will often guide further diagnostics and management. In two-thirds of cases of SE, an acute cause or precipitating factor, such as systemic metabolic derangement, alcohol or other drug abuse, head trauma, infection, or a cerebral lesion, such as a stroke or tumor, and hypoxia, can be identified. Therefore, part of the evaluation of patients in status epilepticus is determining the probable cause.

There are various diagnostic approaches/methods to this type of patient. Most importantly is the historical information that may provide clues as to the etiology of the seizure and guide further work-up and management. Important inquiries to make about the patient’s history include prior seizures or diagnosis of epilepsy, antiepileptic medication compliance, systemic or intracranial malignancies, infections, metabolic disorders, toxic ingestions, alcohol use, and recent falls or head injuries.

A. History Part I: Pattern Recognition:

There are many specific questions that should be asked prior to the workup in order to facilitate treatment and discover the etiology. The following questions should be considered:

a. Does the patient have a history of epilepsy/seizure disorder?

(Most studies have shown that about 40% of patients with SE have a history of epilepsy. However, with NCSE most patients are often middle-aged or elderly and usually have no past history of seizures.)

b. If yes, is the patient on anti epileptic drugs (AEDs)? Compliant? Missed doses?

c. Has the patient been febrile or is there evidence of any recent infection?

d. History of trauma, stroke?

e. Recent alcohol/drug usage?

In the setting of presumed treated SE, or after a witnessed seizure episode, it is important to consider questions such as whether the patient is “more confused than usual” or “inappropriately lethargic”.

B. History Part 2: Prevalence:

In the general population, it has an incidence of about 10 per 100,000 person per year; approximately a quarter of all cases of SE. NCSE is not an uncommon finding in the intensive care setting. Risk factors for NCSE include history of prior epilepsy, coma, age less than 18 years, and earlier convulsive seizures. Children and elderly have a high prevalence for NCSE. Furthermore, patients with acute neurological injury, such as stroke, subarachnoid hemorrhage, anoxic brain injury, meningitis or encephalitis, and brain tumors, are at particular risk. There have been various studies that have shown approximately 20-30% of monitored patients to have been in NCSE.

C. History Part 3: Competing diagnoses that can mimic Non-Convulsive Status.

Nonconvulsive seizures are generally difficult to recognize and tend to be more common than suspected. In certain situations, there may not be an acute or sudden change in the patient’s presentation. NCSE can also be mistaken or confused with various medical states. An acute encephalopathy secondary to metabolic/toxic cause or a hypoglycemic state are a few examples. Organ failure or delirium related to drugs, alcohol or infectious process can also present as possible NCSE.

With someone who has a history of epilepsy, NCSE can be mistaken for a postictal state. Furthermore, psychiatric disorders, such as acute psychosis and catatonia can mimic NCSE. Additionally, syncope, an atonic loss of consciousness, is a common condition that many times is mistaken for a seizure episode. It has also been mistaken for TIA or stroke, which can also present with a focal neurological deficit, alteration of consciousness, or altered mental status that is also commonly confused for NCSE. The complete opposite situation can occur as well. A patient can present with alteration in behavior and may be evaluated and managed as acute delirium, TIA or stroke. However, the cause of his/her presentation may be entirely due to NCSE. Once again this demonstrates the challenge of accurate diagnosis and need for prompt evaluation and management in any elderly person that presents with confusion or change in mental status.

Additionally, NCSE is commonly found in the setting following supposed control of convulsive or other SE, despite presumed adequate treatment. If at any time following the treatment of CSE, the individual does not return to baseline or presents with a persistent neurologic dysfunction, NCSE should be considered until proven otherwise.

D. Physical Examination Findings.

There are important physical exam findings that can help in the diagnosis and direct management. This condition is difficult to diagnose clinically and frequently goes unrecognized. With SE, the onset is generally abrupt, and all patients show altered mentation and behavioral changes that typically last for days to weeks. The clinical signs of NCSE are not merely the abnormal behavior, but its change from a baseline state. Often, family members or caregivers are the first to spot particular changes that might escape the attention of hospital personnel. Patients with NCSE sometimes present with bizarre behavior, change in affect, hallucinations, paranoia or even catatonia.

A psychiatric diagnosis is often the first consideration. Patients in nonconvulsive status are characteristically alert, with constricted or flat affect, and the absence of stupor or coma contributes to misdiagnosis. Dementia, stroke or metabolic/toxic encephalopathy should be considered when memory loss, disorientation, and mood changes predominate. However, NCSE should also be considered as part of the differential. A basic neurological exam to determine focality of neurologic dysfunction should be performed in order to help localize the lesion. However, this may pose a difficult task with comatose or unresponsive patients.

In the comatose patient, examination findings may be overly discrete or too few to reliably follow in order to assess brain injury. Focal SE confined to non-motor areas of the brain may be particularly deceptive. Nonconvulsive seizures and NCSE can have subtle presentations and include minimal movements of the face or eyes, such as sustained eye deviation, blinking, nystagmus, or hippus. In the appropriate clinical settings, such movements are highly suggestive of NCSE.

NCSE can also present itself with speech problems. For example, SE that arises in the opercular region can present as speech difficulties due to dysarthria rather than aphasia. Furthermore, a fundoscopic exam may show papilledema or signs of increased intracranial pressure that can indicate hemorrhage, mass effect, or cerebral edema inciting NCSE. A dilated pupil or dysconjugate gaze can also suggest such evidence, which should all be considered as precipitating factors for NCSE.

E. What diagnostic tests should be performed?

An EEG should be used as the fundamental tool. Making the diagnosis based on EEG findings has posed a complex and controversial issue. In particular, a tremendous variety of EEG samples have been offered as supporting a diagnosis of NCSE in scores of cases in the medical literature. Ictal patterns can be demonstrated on EEG.

In a wide variety of cases, three typical features have been shared in NCSE, including 1) epileptiform spike or sharp wave discharges, 2) generalized or focal slowing and 3) a rapid, rhythmic appearance and frequency that usually is 1 to 3.5 Hz. A neurologist, specifically epileptologist, should be the physician reviewing the EEG in order to help make the diagnosis and proceed with treatment. However, the diagnosis is always made on the entire picture of clinical presentation, findings and EEG.

1. What laboratory studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

There are no specific laboratory studies to identify NCSE. Various labs can be done to provide clues to the etiology of the patient’s presentation. These studies are usually normal, but occasionally they identify a cause for the NCSE, such as nonketotic hyperglycemia, electrolyte imbalance or drug toxicity.

An infectious and metabolic workup should be considered including: CBC, urine analysis and culture, complete metabolic panel, calcium, magnesium, phosphate, toxicology screens, serum alcohol level, and finger-stick glucose. If clinically indicated, a lumbar puncture can be done to evaluate for blood, infection, or abnormal cells. It is always indicated if a patient presents with SE and signs of infection or unknown etiology of SE.

2. What imaging studies (if any) should be ordered to help establish the diagnosis? How should the results be interpreted?

Imaging modalities, including computed tomography (CT) and magnetic resonance imaging (MRI) of the brain, can help discover the etiology of the NCSE, and provide a clue to the actual diagnosis. A CT scan of the brain without contrast should be used to evaluate for hemorrhage, mass, or mass effect.An MRI can be used to evaluate for stroke, tumor, mass lesion/infectious process, or edema. Yet, most importantly, the patient’s history, physical exam and suspected etiology should guide diagnostic image study. If the patient is too unstable to obtain either of these studies, then they should be treated as NCSE until proven otherwise.

F. Over-utilized or “wasted” diagnostic tests associated with this diagnosis.

A prolactin level can be drawn but may be considered an over-utilized test if not done at the appropriate time or a baseline level is unknown. In patients with known epilepsy and subtherapeutic drug levels secondary to noncompliance, certain image modalities such as an MRI may not be needed and can be considered a waste of resources, especially if the patient returns to baseline once the drug levels are corrected.

III. Default Management.

If a patient presents initially in a certain manner that the history and physical indicates the possibility of NCSE, a trial with benzodiazepines can be used to see if the patient’s presentation improves. With suspected NCSE, a trial of benzodiazepines should always be attempted first. The goal is to get the patient to return to a baseline mental status or to resolve the presenting neurological dysfunction.

A. Immediate management.

The duration of status epilepticus is a risk factor for mortality, therefore treatment should be given early in the course.

The main aims of treatment are (1) to support vital functions, (2) to identify and treat causal or precipitating factors, and (3) to terminate ictal activity.

After a period of more than 5 minutes of continuous seizure activity or 1 seizure where the patient has not returned to baseline, oxygen supplementation should be given, obtain patent airway and begin cardiac and oxygen continuous monitoring immediately. First and foremost, the physician must assess and support the patient’s airway, breathing and circulation before any treatment can begin. Intravenous (IV) access should be established so that blood can be taken to determine levels of glucose, electrolytes and drugs, liver and kidney function, as well as complete blood count should be checked.

After obtaining IV access start normal saline IV fluids and provide thiamine 100mg IV plus 50 mL of 50% dextrose IV immediately. The aggressiveness of therapy and the drug chosen for treatment depends on the SE type (e.g., generalized tonic clonic versus absence SE), the age, the comorbidity and the prognosis of the patient. A benzodiazepine should always be given as the first-line treatment. Lorazepam (Ativan) is the preferred therapy because of its efficacy, longer duration and lower risk of seizure recurrence. 0.1mg/kg IV push of lorazepam at a rate no greater than 2mg/min should be given immediately. The physician should continue to repeat lorazepam pushes if seizure persists, with close monitoring of airway and respiratory drive. (If no IV access obtained, the physician can give diazepam per rectum.)

After approximately 5-10 minutes, if the seizure has not subsided, or the patient has not returned to baseline, patient needs to be loaded with an anti-epileptic drug (AED). Fosphenytoin (20 mg PE/kg) IV at a rate less than 150 mg PE/min can be given. Phenytoin (20mg/kg) IV can also be used if Fosphenytoin is not available. However, Phenytoin can only be given at a rate no faster than 50mg/min with cardiac and blood pressure monitoring. Additional fosphenytoin or phenytoin can be given up to a maximum total dose of 30mg/kg if seizure persists.

After 30 minutes, patient may likely need to be intubated if still seizing or has not returned to baseline. Multiple different agents can be used once the patient is intubated to control the seizures. Phenobarbital can be used as a slow push at 20mg/kg at a rate less than 100 mg/min. Midazolam can be given IV at 0.2 mg/kg over 20-30 sec. and Midazolam drip should then be started at 0.05 mg/kg/h up to 2.0 mg/kg/hr.

Lastly, propofol is another common agent that is used for sedation and seizure cessation. Firstly, a bolus of 1-2 mg/kg IV can be given. Then a continuous infusion should be started at 2 mg/kg/h initially and continued anywhere from 1-5 mg/kg/hr.

By this time an urgent EEG should be obtained in order to evaluate for the continuation of seizure activity, especially because NCSE may have developed from CSE.

If a patient presents initially in a certain manner that the history and physical indicates the possibility of NCSE, a trial with benzodiazepines can be used to see if the patient’s presentation improves. NCSE after known GCSE has been found to be even more refractory to treatment in certain cases. In one large series, only 60% of patients with NCSE had an initial response to benzodiazepines. Determining the long-term risk of prolonged NCSE has not been fully studied. However, in several studies, the delay in diagnosis and treatment was associated with significantly more morbidity and mortality. It is difficult to discern whether the concomitant systemic factors such as infection, metabolic disturbances, hypotension and medications may have predominantly caused or influenced the final outcome.

At least in several animal studies, there is a large body of evidence that demonstrates prolonged seizures, even nonconvulsive, can lead to neuronal damage. Seizures can place increased metabolic, oxidative and excitotoxic stress on an already injured brain leading to irreversible injury. Therefore, patients with suspected NCSE should be treated quickly. Treatment for NCSE is much like CSE. Benzodiazepines are usually first line treatment in attempt to interrupt NCSE and are often successful.

For the resistant cases, intravenous phenytoin or phenobarbital has been used. In the case of NCSE that has developed from CSE, the physician will just need to increase the AED dosage the patient is already on or at times add another AED, until there is clinical improvement and or electroencephalographic evidence that the NCSE has seized. Most epileptologist re-treat with higher doses of definitive treatment, or for longer periods at doses that were successful earlier, and then have more antiepileptic drugs (or higher levels of other antiepileptic drugs) on board.

B. Physical Examination Tips to Guide Management.

As mentioned before, the goal of treatment is returning the patient to their baseline mental status or observing the termination of the presenting neurological dysfunction. Most common symptoms to watch for are pupillary changes, resolution of nystagmus or certain automatisms, and state of consciousness.

C. Laboratory Tests to Monitor Response To, and Adjustments in, Management.

The duration of treatment and monitoring has also been inadequately studied. It is important to follow the EEG during prolonged treatment of SE in the ICU; especially when NCSE follows GCSE. Continuous EEG (cEEG) monitoring should be used and seizure activity should be suppressed for a significant amount of time. Many investigators use at least 12-24 hours of seizure or EEG suppression. Medications can then be tapered off over an additional 12-24 hours. However, each regimen should be tailored individually and may require prolonged monitoring depending on the inciting factor. cEEG monitoring is especially useful in evaluating the response to treatment. It is helpful for adjusting infusion rates while avoiding adverse drug effects such as over-sedation and hypotension.

Unfortunately, many of the medications used to stop SE have adverse side effects including sedation, respiratory depression and hypotension, especially, benzodiazepines, phenytoin and phenobarbital. All can decrease respiratory drive requiring mechanical ventilation once initiated at high doses. Moreover, barbiturates as well as phenytoin and phenytoin derivates cause significant hypotension and arrhythmias.

The patient should immediately be transferred to an ICU setting with continuous monitoring when the slightest index of suspicion of SE occurs. He/she should be placed a cardiac monitor and oxygen saturation should be monitored continuously, with a low threshold for intubation and mechanical ventilation. Patient would definitely be intubated once any of the continuous infusions is started, including phenobarbital, midazolam, or propofol drip. Propofol infusion syndrome can occur in some patients, leading to cardiac failure, hyperkalemia, rhabdomyolisis and lipemia. The risk of propofol infusion syndrome is reduced by using doses less than 5mg/kg/hr.

IV levetiracetam (keppra), valproate (depakote) and lacosamide (vimpat) are sometimes used as second-line drugs since they do not cause significant cardiac or respiratory side-effects. However, there is limited evidence regarding their efficacy. Nevertheless, primarily levetiracetam and depakote have been widely used and have been proven to be appropriate in the setting of SE with awake patients or whom the other AEDs mentioned above are contraindicated. With high doses of valproate, cardiac, respiratory and blood pressure monitoring should be performed as well. Pancreatitis, hepatotoxicity and thrombocytopenia can occur; therefore, amylase, lipase, liver function tests and complete blood cell counts should be monitored.

Levetiracetam is generally well-tolerated, and since it is renally excreted dose, should be reduced for patients with impaired kidney function.

D. Long-term management.

Once the patient’s mental status returns to baseline, this is usually a good clinical indicator that he/she is no longer in SE. EEG would also demonstrate the cessation of epileptic discharges or return to normal brain activity. Once it is confirmed that the patient is no longer in SE, and the AED used terminates the SE, then it should be continued and used as prophylaxis. Otherwise, if propofol or midazolam gtt was used to treat the status, then an AED should be initiated and used until patient is seizure free for an extended period of time.

While administering medications such as phenytoin or Phenobarbital, it is important to check levels in order to avoid relapse and recurrent SE. Additionally, it is important to determine that the drug used is in a therapeutic range in order to ensure accurate management and to avoid toxicity. Once a therapeutic level is reached and patient has returned to baseline, then there is no need to check levels daily unless there is a change in clinical status.

At time of discharge, if phenobarbital is continued, a CBC should be regularly checked, for it may cause aplastic anemia in rare cases. This as well can be checked every 6 months if stable at discharge. Most of the medications mentioned prior can associated with somnolence, fatigue, cognitive slowing, dizziness, blurry vision and ataxia, especially at toxic levels. The physician should also be aware of possible drug interactions in the case of polytherapy. Both, phenytoin and phenobarbital, utilize the cytochrome P450 monooxygenase system which can induce or inhibit other medications that are also metabolized by the liver, therefore causing subtherapeutic or toxic levels of certain drugs.

If any AED is started and continued on a female patient of child-bearing age, she must be educated on the teratogenicity of these medications. The AED associated with the most risk is Valproate and is generally avoided in females of child-bearing age unless there is an overwhelming reason for its use; for example, seizures are unresponsive to all other agents. Folic acid supplementation should be started immediately and a form of birth control should be initiated.

E. Common Pitfalls and Side-Effects of Management.

The most common pitfall is failure to recognize, which in turn delays diagnosis as well as adequate treatment NCSE.

The following are certain scenarios in which this may happen:

-Obtundation attributed to alcohol or drug intoxication

-Bizarre behavior or unresponsiveness that is presumed psychogenic in nature

-Hallucinations or agitation mistaken for delirium or psychosis

-Lethargy/confusion attributed to postictal state

-Sudden focal weakness, or aphasia, attributed to stroke

In certain circumstances, witnessed seizures or GCSE may cease, and the patient is presumed to be postictal. At these times, some physicians might make the mistake of not obtaining an EEG or assume the patient’s presentation is secondary to sedating effects of the medications and falsely assume the patient has been adequately treated. However, there are many situations where the patient may have progressed into NCSE, and needs further aggressive management and treatment. With earlier detection and better monitoring of treatment, morbidity and mortality associated with status epilepticus should be properly reduced.

IV. Management with Co-Morbidities.

The management will vary depending on the AED used and the individual co-morbidities of each patient. AEDs which are enzyme inducers will have interactions with other medications used for other medical problems and if not recognized can lead to failure of therapeutic effects of either group of medications.

With certain AEDs, liver and renal function may need to be checked regularly. The drug of choice may need to be changed depending on the co-morbidity. For instance, in patients with renal impairment, the does of levetiracetam, a renally excreted AED has to be changed to a renal dose to prevent toxic effects.

With no acute brain injury or known seizure history, an AED may not have to be continued. For example, in a patient who develops NCSE secondary to benzodiazipine withdrawal, an AED for future management is not indicated. Therefore, there will be no change in standard management.

The long-term management of NCSE depends entirely on the precipitating factor. In an individual with known epilepsy, an AED will be continued. If the individual has hepatic dysfunction, then an AED that is metabolized and cleared by the kidneys, such as levetiracetam can be used instead. Newer agents like zonisamide and lacosamide are less hepatotoxic and can be considered as well. Furthermore, with renal impairment, levetiracetam can still be used but a smaller dose may be needed.

A. Renal Insufficiency.

When levetiracetam is used, renal function should be checked prior to and during the use since it is metabolized and excreted by the renal system. A levetiracetam level can be checked as well, however, it is usually a send out lab and may take a few days to return. As mentioned previously, if renal disease exists, levetiracetam may still be used since it is not necessarily nephrotoxic, but a lower dose may be needed.

B. Liver Insufficiency.

Liver function tests should be routinely checked since most medications are metabolized by the liver and can be hepatotoxic in certain situations. With stable liver function at time of discharge, LFTs can be checked every 6 months. If LFTs increase three times their baseline number then cessation is warranted and another AED should be used.

With the risk of recurrent SE, it is safest to start another AED first and reach a therapeutic level of that medication before weaning off any AED.

C. Systolic and Diastolic Heart Failure.

No significant change in management is needed. However, the physician should be aware of possible drug interactions in the case of polytherapy. For example, phenytoin and phenobarbital utilize the cytochrome P450 monooxygenase system which can induce or inhibit other medications that are also metabolized by the liver, therefore causing subtherapeutic or toxic levels of certain drugs.

D. Coronary Artery Disease or Peripheral Vascular Disease.

No significant change in management is needed. However, the physician should be aware of possible drug interactions in the case of polytherapy. For example, certain medications utilize the cytochrome P450 monooxygenase system which can induce or inhibit other medications that are also metabolized by the liver, therefore causing subtherapeutic or toxic levels of certain drugs.

E. Diabetes or other Endocrine issues.

No significant change in management is needed. However, the physician should be aware of possible drug interactions in the case of polytherapy.

F. Malignancy.

If phenobarbital or carbamazepine is used, a CBC should be regularly checked, for it may cause aplastic anemia in rare cases. This as well can be checked every 6 months if stable at discharge. The drug-drug interactions should be checked prior to administration and discharge to avoid toxicity or adverse interactions.

G. Immunosuppression (HIV, chronic steroids, etc).

Please refer above to the Malignancy section.

H. Primary Lung Disease (COPD, Asthma, ILD).

No significant change in management is needed. However, the physician should be aware of possible drug interactions in the case of polytherapy.

I. Gastrointestinal or Nutrition Issues.

No significant change in management is needed. However, the physician should be aware of possible drug interactions in the case of polytherapy.

J. Hematologic or Coagulation Issues.

If phenobarbital or tegretol is used, a CBC should be regularly checked, for it may cause aplastic anemia in rare cases. Additionally, the physician should be aware of possible drug interactions in the case of polytherapy.

K. Dementia or Psychiatric Illness/Treatment.

Additional side effects of keppra that can occur include irritability, mania, psychosis, especially if the individual has an underlying psychiatric illness. If any of these changes do occur, keppra should be weaned off while starting another AED.

V. Transitions of Care.

A. Sign-out considerations While Hospitalized.

Sign-out depends on the clinical state of the patient and precipitating factors that lead to NCSE. The patient initially should remain on continuous EEG monitoring unless clinically has returned to baseline. Important factors that should be addressed include drug of choice, drug levels, respiratory and cardiac status of the patient. Levels should be checked, and if noted to be subtherapeutic, medication can be re-loaded or dosages should be increased until therapeutic range has been achieved.

With the use of most intravenous AEDs or drips discussed prior, the patient should remain on continuous cardiac and respiratory monitoring and in the ICU. Lorazepam pushes can be used as needed for breakthrough seizure activity that lasts more than 2 minutes.

Side effects of each medication, mentioned above, should be discussed with the physician covering so appropriate monitoring is ensured. It is important to remember that no AED should be abruptly discontinued since the risk of recurrent status epilepticus is high. Prior to cessation, another AED should be started, and after 3-4 doses (or steady-state) have been achieved the initial AED should then be tapered off slowly. This process should also be performed while the patient is on continuous EEG monitoring.

B. Anticipated Length of Stay.

Length of stay can vary depending on the initiating factor and the duration of SE. Once the patient is no longer in status and has clinically returned to baseline, they should be monitored closely until seizure-free for at least 24-48 hours prior to discharge from the ICU. The AED used for preventive measures should be at a therapeutic range, and all baseline labs should be obtained at time of discharge.

C. When is the Patient Ready for Discharge.

The duration of treatment and monitoring has also been inadequately studied. It is important to follow the EEG during prolonged treatment of SE in the ICU; especially when NCSE follows GCSE. Continuous EEG (cEEG) monitoring should be used and seizure activity should be suppressed for a significant amount of time. Many investigators use at least 12-24 hours of seizure or EEG suppression. Medications can then be tapered off over an additional 12-24 hours. However, each regimen should be tailored individually and may require prolonged monitoring depending on the inciting factor. It is important to determine that the drug used is in a therapeutic range in order to ensure accurate management and to avoid toxicity. The patient should be safe for discharge, once a therapeutic level is reached and patient has returned to baseline.

D. Arranging for Clinic Follow-up.

The patient should follow-up with his/her PCP and the neurologist who cared for him/her during their hospitalization.

1. When should clinic follow up be arranged and with whom.

The patient should follow-up with his/her PCP within 1-2 weeks after discharge and with the neurologist within at least 4-6 weeks from discharge.

2. What tests should be conducted prior to discharge to enable best clinic first visit.

It is important to determine that the drug used is in a therapeutic range in order to ensure accurate management and to avoid toxicity. Additionally, depending on the drug of choice used, LFTs should be checked if hepatically cleared, chem 7, if renally cleared and a baseline CBC when using drugs such as phenobarbital and tegretol. (Please refer above IIIc, laboratory tests to monitor management.)

3. What tests should be ordered as an outpatient prior to, or on the day of, the clinic visit.

Important labs that should be ordered prior to follow-up are AED levels, depending on the drug of choice, LFTs should be checked if the AED is hepatically metabolized or cleared. Examples are phenytoin/dilantin, phenobarbital, and valproate. With Phenobarbital, a CBC should be checked as well prior to follow-up in order to monitor and prevent aplastic anemia. Furthermore, if levetiracetam is used, renal function should be monitored prior to discharge and at follow-up. A levetiracetam level can be checked as well.

If AED levels are therapeutic at initial follow-up visit then repeat levels do not need to be rechecked unless another seizure episode occurs or the patient starts experiencing side effects from the specific medication. As mentioned before, most of the medications used can also cause somnolence, dizziness, ataxia, blurry vision, especially at supratherapeutic levels. More than likely, an MRI/CT scan as well as an EEG will have been done during hospitalization and prior to discharge. A repeat EEG may be helpful prior to follow-up with the neurologist.

E. Placement Considerations.

Placement considerations are determined based on the concomitant disease state of the patient and the precipitating factors. If the patient has suffered an anoxic injury or ischemic or hemorrhagic stroke they may need to go to an LTAC or SNF. Placement can only be determined based on the individual patient and their situation. They should be evaluated by physical and occupational therapy in order to determine individual needs and to facilitate appropriate placement and future care.

F. Prognosis and Patient Counseling.

It is difficult to determine prognosis and outcome secondary to the immense variety of illnesses that are associated with the complexity of NCSE. Prognosis for each type along with its associated initiating factors, varies tremendously, with etiology being the most important prognostic feature. Patients, especially in the ICU, are still subject to the effects of the underlying illness that may have initially prompted the ICU admission.

The exact long-term risk from an episode of NCSE, without an acute brain lesion, is unclear. However, morbidity and mortality can be substantial with secondarily generalized NCSE in the setting of severe medical or neurological disease. High mortality was associated in cases where acute symptomatic brain insult was the cause of SE. Continuous EEG monitoring can help provide prognostic information especially after brain injury. In comatose patients, prolonged monitoring can assess factors such as sleep architecture, epileptiform discharges and reactivity, all which help determine prognosis.

Certain patterns, such as alpha coma and burst suppression after cardiac arrest have often been associated with lack of neurologic recovery. For instance, the absence of sleep architecture, in patients with traumatic brain injury (TBI), has also been found to be a poor predictor. Certain studies have shown that CSE and NCSE after cardiac arrest were associated with less than a 25% chance of good neurologic outcome. However, there have been some reports that showed few long-term sequelae from NCS itself. Although most of these case were not ICU cases, no significant mortality or cognitive morbidity accrued from the SE, suggesting that morbidity must come from the underlying etiology, not from the SE itself.

VI. Patient Safety and Quality Measures.

A. Core Indicator Standards and Documentation.

NA

B. Appropriate Prophylaxis and Other Measures to Prevent Readmission.

AED levels, when possible, should be obtained prior to discharge and should be in therapeutic range. At follow-up they should be checked if symptoms recur in order to prevent a relapse of CSE or NCSE. If complaints of somnolence, dizziness, ataxia or blurry vision occur then levels should be checked to avoid toxicity, for some AEDs at toxic levels can actually cause or lower seizure threshold.

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