Status Epilepticus

Wuhan university zhongnan hospital Emergency department Xiaoqing jin

Definition
two or more sequential seizures without full recovery of consciousness between seizures, or more than 30 minutes of continuous seizure activity Practically speaking, any person who exhibits persistent seizure activity or who does not regain consciousness for five minutes or more after a witnessed seizure should be considered to have status epilepticus

Classification scheme
Generalized (tonic-clonic, myoclonic, absence, atonic, akinetic) and partial (simple or complex) status epilepticus generalized status epilepticus (overt or subtle) and nonconvulsive status epilepticus (simple partial, complex partial, absence)

EPIDEMIOLOGY
69 percent of episodes in adults and 64 percent of episodes in children were partial onset generalized status epilepticus in 43 percent of adults and 36 percent of children

DeLorenzo RJ, Hauser WA, Towne AR, Boggs JG, Pellock JM, Penberthy L, et al. A prospective, population-based epidemiologic study of status epilepticus in Richmond, Virginia. Neurology 1996;46:1029-35.

 Among adults, patients older than 60 had the highest risk of developing status epilepticus, with an incidence of 86 per 100,000 persons per year. Among children 15 years or younger, infants younger than 12 months had the highest incidence and frequency of status epilepticus

Hesdorffer DC, Logroscino G, Cascino G, Annegers JF, Hauser WA. Incidence of status epilepticus in Rochester, Minnesota, 1965- 1984. Neurology 1998;50:735-41.

 In adults, the major causes were low levels of antiepileptic drugs (34 percent) and cerebrovascular disease (22 percent), including acute or remote stroke and hemorrhage

Cascino GD, Hesdorffer D, Logroscino G, Hauser WA. Morbidity of nonfebrile status epilepticus in Rochester, Minnesota, 1965-1984. Epilepsia 1998;39:829-32.

Leading causes of status epilepticus

Etiology of Status Epilepticus

 The reported annual frequency of cases in the United States has been between 102,000 and 152,000.with roughly 55,000 of these incidents proving fatal estimates of mortality range from 17% to 23% and morbidity from 10% to 23 %

The primary determinants of mortality in persons with status epilepticus were

duration of seizures age at onset and etiology

 Patients with anoxia and stroke had a very high mortality rate that was independent of other variables. Patients with status epilepticus occurring in the setting of alcohol withdrawal or low levels of antiepileptic drugs had a relatively low mortality rate

Systemic Pathophysiology

Pathophysiology
Postmortem studies indicate that the key anatomic structures involved in the pathogenesis of SE are
the hippocampus associated limbic system hypertension lactic acidosis and tachycardia

Prolonged SE (ie, beyond 60 minutes) may be associated with

hyperthermia hypoglycemia hypotension pulmonary edema renal failure

Early manifestations (ie, during the first 30 minutes of SE)

cardiac arrhythmia hyperglycemia

 Once a diagnosis has been established, treatment should follow Assess airway, breathing, and circulation Stop the seizure Find the underlying cause Correct it

Management of Status Epilepticus

The first step assessing the patients airway and oxygenation Necessary interventions include maintaining oxygenation and circulation, assessing the etiology and laboratory evaluations, obtaining intravenous access, and initiating drug therapy

aspects to the general management of SE

Airway If the clinical seizure activity terminates and it is safe to access the oropharynx, a Guedel (or nasopharyngeal) airway may be useful to maintain oropharyngeal patency

Intubation Intubation is generally needed during infusion therapies If intubation is necessary but difficult, use temporary non-depolarizing neuromuscular junction blockade for intubation (eg, vecuronium) Otherwise, muscle paralytics are typically not used in the management of SE

Hypertension Ensure volume replacement and use vasopressors if needed. Do not treat hypertension unless critical

Hyperglycemia Ensure glycemic control because hyperglycemia may exacerbate neuronal injury Cerebral edema Treat hyperventilation with mannitol or steroids, depending on etiology, if evident

Acidosis Acidosis usually parallels the degree of anaerobic metabolism and generally resolves with seizure control or intubation with general anesthesia. Boluses of sodium bicarbonate are used exceptionally

Hyperthermia Hyperthermia, like hypertension, generally resolves with control of SE, but external cooling, cool peritoneal lavage, or extracorporeal blood cooling may be used if refractory

Rhabdomyolysis Rhabdomyolysis is an underappreciated morbidity associated with convulsive SE and should be detected and treated early with saline diuresis, urine alkalization, and if needed, muscle paralysis

Maintenance AED therapy All patients with de novo SE or epilepsy-related SE need maintenance AED therapy. Ideally, this should be initiated within the first day of admission, irrespective of the clinical course. the maintenance AED regimen can be modified toward the end of the hospital stay

Electroencephalographic monitoring Ideally, begin EEG monitoring if patient is not waking up 15 minutes after clinical movements have stopped

Medications

Diazepam
Enters the brain rapidly because of its high lipid solubility, after 15 to 20 minutes it redistributes to other areas of the body, reducing its clinical effect Despite its fast distribution half-life, the limination half-life is approximately 24 hours. Thus, sedative effects potentially could accumulate with repeated administration

Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med 2001;345:631-7.

 Diazepam in a typical intravenous dosage of 5 to 10 mg per minute terminates seizures of any type in about 75 percent of patients with status epilepticus Adverse effects include respiratory suppression hypotension sedation and local tissue irritation

Shaner DM, McCurdy SA, Herring MO, Gabor AJ. Treatment of status epilepticus: a rospective comparison of diazepam and phenytoin versus phenobarbital and optional phenytoin. Neurology 1988;38:202-7.

Lorazepam
Lorazepam differs from diazepam in two important respects
a longer duration of action It is less lipid-soluble than diazepam, with a distribution half-life of two to three hours versus 15 minutes for diazepam. Therefore, it should have a longer duration of clinical effect. Lorazepam also binds the GABAergic receptor more tightly than diazepam, resulting in a longer duration of action The anticonvulsant effects of lorazepam last six to 12 hours, and the typical dose ranges from 4 to 8 mg. This agent also has a broad spectrum of efficacy, terminating seizures in 75 to 80 percent of cases. Its adverse effects are identical to those of diazepam

PHENYTOIN
The main advantage of phenytoin is the lack of a sedating effect adverse effects may accompany intravenous administration Arrhythmias and hypotension local irritation phlebitis dizziness

FOSPHENYTOIN
Fosphenytoin is a water-soluble prodrug of phenytoin that completely converts to phenytoin following parenteral administration. Like phenytoin, fosphenytoin is useful in treating acute partial and generalized tonic-clonic seizures Fosphenytoin is converted to phenytoin within eight to 15 minutes
Ramsay RE, DeToledo J. Intravenous administration of fosphenytoin:options for the management of seizures. Neurology 1996;46(6 Suppl 1):S17-9

 The initial dose of fosphenytoin is 15 to 20 mg PE per kg, so it can be infused at a rate as high as 150 mg PE per minute, a rate of infusion that is three times faster than that of intravenous phenytoin

 Adverse effects that are unique to fosphenytoin include perineal paresthesia and pruritus; however, both are related to higher rates of administration Unlike phenytoin, fosphenytoin does not cause local irritation. Intravenous therapy has been associated with hypotension, so continuous cardiac and blood pressure monitoring are recommended

PHENOBARBITAL
The normal loading dose is 15 to 20 mg per kg. Because highdose phenobarbital is sedating, airway protection is an important consideration, and aspiration is a major concern. Intravenous phenobarbital also is associated with systemic hypotension

VALPROATE
It has a broad spectrum of efficacy and may be useful in patients with absence or myoclonic status epilepticus. Adverse effects include local irritation, gastrointestinal distress, and lethargy

Protocol for Management of Status Epilepticus

At: zero minutes

Initiate general systemic support of the airway (insert nasal airway or intubate if needed)
Check blood pressure Begin nasal oxygen Monitor ECG and respiration Check temperature frequently Obtain history Perform neurologic examination

 Send sample serum for evaluation of electrolytes blood urea nitrogen glucose level complete blood cell count toxic drug screen and anticonvulsant levels check arterial blood gas values Start IV line containing isotonic saline at a low infusion rate

 Inject 50 mL of 50 percent glucose and 100 mg of thiamine IV or IM Call EEG laboratory to start recording as soon as feasible Administer lorazepam at 0.1 to 0.15 mg per kg IV (2 mg per minute); if seizures persist, administer fosphenytoin at 18 mg per kg IV (150 mg per minute, with an additional 7 mg per kg if seizures continue)

At: 20 to 30 minutes, if seizures persist

Intubate, insert bladder catheter, start EEG recording, check temperature Administer phenobarbital in a loading dose of 20 mg per kg IV (100 mg per minute)

At: 40 to 60 minutes, if seizures persist

Begin pentobarbital infusion at 5 mg per kg IV initial dose, then IV push until seizures have stopped, using EEG monitoring; continue pentobarbital infusion at 1 mg per kg per hour; slow infusion rate every four to six hours to determine if seizures have stopped, with EEG guidance; monitor blood pressure and respiration carefully. Support blood pressure with pressors if needed

or Begin midazolam at 0.2 mg per kg, then at a dosage of 0.75 to 10 mg per kg per minute, titrated to EEG monitoring or Begin propofol at 1 to 2 mg per kg loading dose, followed by 2 to 10 mg per kg per hour. Adjust maintenance dosage on the basis of EEG monitoring