Status EpilepticusStatus Epilepticus

Maria B. Weimer, MDMaria B. Weimer, MD

LSUHSC NeurologyLSUHSC Neurology

DefinitionDefinition

Prolonged seizure activity lasting greater Prolonged seizure activity lasting greater than 30 minutes than 30 minutes

Or, recurrent seizures without the interval Or, recurrent seizures without the interval of recovery (consciousness) lasting of recovery (consciousness) lasting greater than 30 minutes greater than 30 minutes

RememberRemember

Most seizures are brief, lasting less than 5 Most seizures are brief, lasting less than 5 minutesminutes

If a seizure is lasting greater than 10 If a seizure is lasting greater than 10 minutes, are likely to be prolongedminutes, are likely to be prolonged

EpidemiologyEpidemiology

1/3 cases are due to acute insults to the 1/3 cases are due to acute insults to the brain, including meningitis, encephalitis, brain, including meningitis, encephalitis, head trauma, hypoxia, hypoglycemia, drug head trauma, hypoxia, hypoglycemia, drug intoxication or withdrawalintoxication or withdrawal

1/3 cases have a history of chronic 1/3 cases have a history of chronic epilepsy or febrile convulsionsepilepsy or febrile convulsions

1/3 of cases of new-onset epilepsy1/3 of cases of new-onset epilepsy

EtiologyEtiology

Idiopathic: no acute precipitating CNS or Idiopathic: no acute precipitating CNS or metabolic insult– normal childmetabolic insult– normal child

Remote Symptomatic: no acute Remote Symptomatic: no acute precipitant, but prior CNS insult known to precipitant, but prior CNS insult known to increase seizure riskincrease seizure risk

Acute Symptomatic: an acute illness with Acute Symptomatic: an acute illness with known CNS insult or metabolic known CNS insult or metabolic disturbancedisturbance

EtiologyEtiology

Progressive Encephalopathy: occurring Progressive Encephalopathy: occurring with a known progressive neurological with a known progressive neurological disease- degenerativedisease- degenerativeFebrile: sole provocation is feverFebrile: sole provocation is feverPrecipitants of SE: stress, sleep Precipitants of SE: stress, sleep deprivation, fever, infections, missed deprivation, fever, infections, missed medications, medications that lower the medications, medications that lower the seizure threshold, menstrual issues, and seizure threshold, menstrual issues, and many othersmany others

PathophysiologyPathophysiology

Animal models with SE have shown Animal models with SE have shown irreversible neuronal damage occurs after irreversible neuronal damage occurs after 30 minutes of continual convulsions30 minutes of continual convulsions

Neuronal damage occurs even when Neuronal damage occurs even when experimental animals are paralyzed and experimental animals are paralyzed and artificially ventilatedartificially ventilated

PathophysiologyPathophysiology

In these animals, in which adequate In these animals, in which adequate glucose levels have been maintained, glucose levels have been maintained, these studies suggest although systemic these studies suggest although systemic complications such as hypoxia, complications such as hypoxia, hypoglycemia, lactic acidosis, and hypoglycemia, lactic acidosis, and especially hyperpyrexia may exacerbate especially hyperpyrexia may exacerbate the damage that results from sustained the damage that results from sustained seizure activity, the seizure itself is a seizure activity, the seizure itself is a substantial contributorsubstantial contributor

MortalityMortality

Determined largely by the underlying Determined largely by the underlying etiology, but may be aggravated by etiology, but may be aggravated by delayed or inadequate treatment which delayed or inadequate treatment which prolongs the duration of the episodeprolongs the duration of the episodeIn past, mortality rates in children have In past, mortality rates in children have ranged from 6-18%ranged from 6-18%More recent studies where patients have More recent studies where patients have been treated aggressively, have mortality been treated aggressively, have mortality of 3-5%of 3-5%

MorbidityMorbidity

In one study, 9% of children suffered new In one study, 9% of children suffered new motor or cognitive deficits following SEmotor or cognitive deficits following SE– However, only 1.5% of the patients with However, only 1.5% of the patients with

unprovoked (remote symptomatic or unprovoked (remote symptomatic or idiopathic) or febrile status sustained idiopathic) or febrile status sustained neurologic sequellae attributable to the SE neurologic sequellae attributable to the SE itselfitself

ClassificationClassification

Generalized Convulsive SE- Generalized Convulsive SE- – 11°° or 2 or 2°° Generalized Generalized– Bilateral tonic and clonic in some combination but not Bilateral tonic and clonic in some combination but not

always symmetricalways symmetric– Consciousness always impairedConsciousness always impaired– Reasonable (but variable) post ictal period Reasonable (but variable) post ictal period – Beware “burn out” - EEG can helpBeware “burn out” - EEG can help– Most common and most dangerousMost common and most dangerous

Absence SE- nonconvulsiveAbsence SE- nonconvulsiveComplex Partial SE- nonconvulsiveComplex Partial SE- nonconvulsiveSimple Partial SESimple Partial SE

TreatmentTreatmentStep 1Step 1

ABCDEABCDE– Maintain Airway- patient at risk for aspirationMaintain Airway- patient at risk for aspiration

– Breathing- place OBreathing- place O22, be ready for intubation, be ready for intubation

– Circulation- obtain IV accessCirculation- obtain IV access– Dextrose: check glucose levelsDextrose: check glucose levels– Electrolytes: check electrolytes (Na, Ca, Mg, Electrolytes: check electrolytes (Na, Ca, Mg,

POPO44), and anticonvulsent levels), and anticonvulsent levels

TreatmentTreatmentMedicationsMedications

Ideal drug for treating SEIdeal drug for treating SE– Rapid entry into CNSRapid entry into CNS– Rapid onset of actionRapid onset of action– Long duration of actionLong duration of action– SafetySafety– Absence of sedationAbsence of sedation– Useful as maintenance AEDUseful as maintenance AED

Treatment Treatment Step 2Step 2

Benzodiazepine TherapyBenzodiazepine Therapy– DiazepamDiazepam– LorazepamLorazepam

DiazepamDiazepam

Highly lipid solubleHighly lipid soluble– Rapid CNS entry- stops seizures in 1-3 minutesRapid CNS entry- stops seizures in 1-3 minutes

Rapid redistribution in fatty tissuesRapid redistribution in fatty tissues– Brain concentrations fall quicklyBrain concentrations fall quickly– Duration of action is 15-30 minutesDuration of action is 15-30 minutes– TT1/21/2= 30 hr= 30 hr

Dose: <3yrs, 0.5mg/kg, >3yrs, 0.3mg/kgDose: <3yrs, 0.5mg/kg, >3yrs, 0.3mg/kg

Side Effects: sedation, decreased respiration Side Effects: sedation, decreased respiration and blood pressureand blood pressure

LorazepamLorazepam

Less lipid soluble than diazepamLess lipid soluble than diazepam– Slower CNS, stops seizures in 6-10 minSlower CNS, stops seizures in 6-10 min

Not as rapidly redistributed to fat storesNot as rapidly redistributed to fat stores– Longer duration of action 12-24 hrLonger duration of action 12-24 hr– TT1/21/2 =14 hr =14 hr

Dose: 0.05—0.1mg/kgDose: 0.05—0.1mg/kg

Side Effects: decreased LOC, respiration and Side Effects: decreased LOC, respiration and BP BP

Treatment Treatment Step 3Step 3

Phenytoin/FosphenytoinPhenytoin/FosphenytoinPhenytoinPhenytoin

IV dosing 20 mg/kg loadIV dosing 20 mg/kg load

Stops seizures in 10-30 minutesStops seizures in 10-30 minutes

Duration of action 24 hrs, T ½=24hrDuration of action 24 hrs, T ½=24hr

Max infusion rate of 1mg/kg/min, max- 50 mg/minMax infusion rate of 1mg/kg/min, max- 50 mg/min

Side Effects: arrhythmias, hypotension, wide QT Side Effects: arrhythmias, hypotension, wide QT interval, phelibitisinterval, phelibitis

pH=11-12, may only give IV or popH=11-12, may only give IV or po

TreatmentTreatmentStep 3Step 3

Fosphenytoin- phenytoin prodrugFosphenytoin- phenytoin prodrugIV dosing: 20 mg/kg loadIV dosing: 20 mg/kg load

Safer than phenytoinSafer than phenytoin

pH=8-9pH=8-9

May give IV or IMMay give IV or IM

May give faster than phenytoin(100-May give faster than phenytoin(100-150mg/min)150mg/min)

Much more expensiveMuch more expensive

Treatment Treatment Step 4Step 4

PhenobarbitalPhenobarbital– Lipid solubility < phenytoinLipid solubility < phenytoin– Duration of action>48 hrs, TDuration of action>48 hrs, T1/2= 1/2= 100 hours100 hours– Dose 20 mg/kgDose 20 mg/kg– Side Effects: sedation, decreased respiration Side Effects: sedation, decreased respiration

and BPand BP– Be ready to intubate!!Be ready to intubate!!

TreatmentTreatmentStep 5Step 5

If you haven’t called Neurology, please call If you haven’t called Neurology, please call us!!!us!!!

Consider IV Valproic Acid (Depacon)Consider IV Valproic Acid (Depacon)– FDA approved only for replacement or oral FDA approved only for replacement or oral

dosingdosing– Rapid loading dose appears safeRapid loading dose appears safe– 25-30mg/kg rapidly infused25-30mg/kg rapidly infused– Side Effects: dizziness, HA, nauseaSide Effects: dizziness, HA, nausea

Consider Keppra IV LoadConsider Keppra IV Load– Off labelOff label– I use 30mg /kg IV x1I use 30mg /kg IV x1

Refractory Status EpilepticusRefractory Status Epilepticus

Intubation, IV accessIntubation, IV access

Continuous EEG monitoringContinuous EEG monitoring

Medication ComaMedication Coma– PentobarbitalPentobarbital– MidazolamMidazolam– PropofolPropofol– Very high dose phenobarbVery high dose phenobarb

Consider the EtiologyConsider the Etiology

PE: focal – mass, traumaPE: focal – mass, trauma

Serum studies: electrolytes, LFTs, CBC, Serum studies: electrolytes, LFTs, CBC, Cx, anticonvulsent levels, Tox screen, Cx, anticonvulsent levels, Tox screen, follow u/a for possible rhabdomyolysisfollow u/a for possible rhabdomyolysis

Neuroimaging: plain CT of head (use Neuroimaging: plain CT of head (use contrast if suspect brain tumor or AVM)contrast if suspect brain tumor or AVM)

Consider the EtiologyConsider the Etiology

LP: necessary for any febrile seizure LP: necessary for any febrile seizure under the age of 18 monthsunder the age of 18 months– Must strongly consider in comatose patient – Must strongly consider in comatose patient –

please check imaging firstplease check imaging first– Remember SE can cause pleocytosis (usually Remember SE can cause pleocytosis (usually

< 20 cells)< 20 cells)– Do not delay antimicrobial therapy if CNS Do not delay antimicrobial therapy if CNS

infection is suspectedinfection is suspected– Consider acyclovir Consider acyclovir

SUMMARYSUMMARY

ABCDEABCDE

Lorazepam (0.1mg/kg) or DiazepamLorazepam (0.1mg/kg) or Diazepam– Give 5 minute interval then may repeatGive 5 minute interval then may repeat

Fosphenytoin: 20mg/kg, may give additional Fosphenytoin: 20mg/kg, may give additional 10mg/kg after initial load10mg/kg after initial load

Phenobarb: 20mg/kg- be ready for intubationPhenobarb: 20mg/kg- be ready for intubation

If neurology not involved, call usIf neurology not involved, call us

Drug ComaDrug Coma