Status Epilepticus: Evaluation and Management

Terms: Seizures and Status Epilepticus


A seizure is paroxysmal disturbance of brain electrical activity. Its onset may be focal or generalized. Focal-onset seizures may or may not become generalized. A clinical seizure is abnormal brain electrical activity that occurs in time locked association with abnormal clinical behavior change. Clinical behavior change can be motor or sensory activity.

Status Epilepticus-Definitions

  • 1903: The maximum development of epilepsy, in which one paroxysm so closely follows another that the coma and exhaustion are continuous between seizures. (Clark and Prout, Am J of Insanity 1903/04; 60:291-306.)
  • 1964: Whenever a seizure persists for a sufficient length of time or is repeated frequently enough to produce a fixed and enduring epileptic condition. (Commission on Terminology ILAE, Epilepsia 1964; 5:297-306.)
  • 1981: Whenever a seizure persist for a sufficient length of time or is repeated frequently enough that recovery between attacks does not occur. (Commission on Terminology ILAE, Epilepsia 1981; 22:489-501.)
  • 1993: Status Epilepticus is two or more seizures without regaining consciousness or a single seizure that last more than 30 minutes. (JAMA 1993; 270:854-859.)
  • 1999: Operational Definition for Children over 5 years and adults: Any seizure lasting more than 5 minutes or two or more discrete seizures between which there is incomplete recovery of consciousness.(Epilepsia 1999; 40: 120-124., Ann Neurol. 49:659-664, 2001.)

Status Epilepticus is a Medical Emergency

The practical definition for Status Epilepticus is: seizures lasting longer than 10 minutes, or seizures on presentation to the Emergency Room, or seizures recurring in the ER. Remember basics of Seizure First Aid.

Types of Status Epilepticus

  1. Generalized
    • Tonic Clonic Status- One focus of this presentation
    • Absence Status
  2. Focal Status
    • Epilepsia Partialis Continua
    • Complex Partial Status
  3. Refractory Status Epilepticus - Another focus of this presentation
    • Defined as status epilepticus lasting longer than 60 minutes despite adequate doses of a benzodiazepine and a second antiepileptic (AED) drug.
    • 9-31% of all status

Incidence of Status Epilepticus

  • 50,000-250,000 times per year in the U.S.
  • 21% are less than 1 year of age
  • 64% are less than 5 years of age
  • 10-25% have more than one episode of status

Status Epilepticus and Epilepsy

Epilepsy is a number of different chronic conditions with recurring episodes of seizures.
  • Less than 50 % of individuals with status epilepticus have a history of Epilepsy
  • 15% of epileptics will have status epilepticus
  • 10% of epileptics present with status epilepticus
Outcome and Etiology are closely linked. Status has much less morbidity in children, except with progressive CNS disease.
Etiology of Status Children Mortality Adults Mortality
Fever (non-CNS infection)
36%
2%
<5%
45%
Idiopathic (afebrile)
24-39%
-
24-38%
-
Chronic neurologic disease
15%
-
10%
-
Metabolic/Toxic
8%
5%
9%
40%
Medication Change
20%
-
19%
8%
Anoxia
5%
8%
11%
65%
CNS infection
5%
-
2%
38%
Tumor
1%
36%
4%
20%
Acute Trauma/Abuse
4%
-
5%
22%
Degenerative Disease
2
-
2
-
Vascular Disease
3%
5%
25%
10%
Compiled from DeLorenzo et. al., Status epilepticus in children, adults, and the elderly.
Epilepsia 1992; 33 (suppl 4): S15-S25.

Causes of Status Epilepticus in Children

Idiopathic 30%
Fever 25%
Acute Symptomatic 35%
Remote Symptomaic 15%
Progressive 5%
Shinnar (1992)

Physiologic Changes with Status, (Meldrum, 1983)

  • Early Changes (less than 60 minutes)
    • Local metabolic abnormalities
    • Reversible 1st 10-60 minutes
  • Late Changes (more than 60 minutes)
    • Increased Temperature
    • Decreased Glucose and Blood Pressure
    • Increased Pulmonary Congestion

Outcome of Status Epilepticus

The most important determinants of outcome for status epilepticus are:
  • Duration of the seizure activity
    Duration of Status Mortality
    Seizure for less than 1 hour
    3%
    Seizure for more than 1 hour
    32%
  • Etiology of the Status influences outcome as well as the need and type of further anti-seizure therapy.
    Etiology of Status Mortality
    Idiopathic
    4%
    Symptomatic
    20%
    (Gilbert et.al., 1999)

    Etiology of Status Risk of Epilepsy Risk of
    Recurrent Status
    Chronic
    AED Rx
    Diastat®
    Idiopathic
    0%
    3%
    No!
    Yes?
    Remote Symptomatic
    ++
    50%
    Yes!
    Yes!
    Febrile
    +
    +
    No?
    Yes?
    Acute Symptomatic
    15-30%
    +
    Yes?
    Yes?
    Progressive
    ++
    50%
    Yes!
    Yes!

Outcome of Status over the Decades

Currently, status epilepticus has 1/5 the morbidity and 1/3 the mortality of pre-1970. Still, morbidity for status in children is at least 3% and as high as 30% in children with refractory status (Sahin et. al., 2001) and 30% in adults. Improvements reflect study referral bias, use of retrospective data, and changes in definitions of status (from greater than 60 minutes to much shorter duration of seizures). The most important factor for improved outcomes is improved care.

Outcome is determined by etiology, age, duration and treatment. You can affect only treatment.

Treatment and Evaluation of Status Epilepticus

Treatment and evaluation begin when the operational diagnosis is made.
  • Injury may begin before the formal criteria for the diagnosis is met.
Treatment and evaluation are performed in parallel time-lines: do not defer treatment until test results return.

Treatment protocols (predetermined therapeutic interventions) are more likely to succeed than impromptu measures.
  • No single protocol is superior - be prepared in advance!
  • IV treatments are favored. Know a drug and be comfortable using that drug. Lorazepam has advantages over diazepam. (Alldredge et al. NEJM 2001)
  • Some approaches are inferior
  • Rectal diazepam gel (Diastat®) may be available in field by EMTs or at home by parents.

The goal of treatment is the cessation of both clinical and electrical seizures.

Evaluation and Treatment of Status Epilepticus

Suggested time line for the evaluation and treatment of Status Epilepticus.

Time
Evaluation
Procedure
0 min
Observe, verify, and describe seizure
VS, pulse oximetry, Dextrostx
EKG/HR monitor, Glucose, Lytes, CBC
AED levels, CRP, ABG
NH3, Tox screen
Airway, O2
Start IV
(Benzodiazepine dose #1
if seizure present on arrival)
3 to 5 min
Labs and oservation
IV fluids, glucose
Benzodiazepine dose #1
(Benzodiazepine dose #2
if seizure present on arrival)
by 10 min
Labs and oservation
Benzodiazepine dose #2
(Lorazepam or Diazepam)
AED # 1
Phenytoin 20 mg / kg IV
Phenobarbital 20 mg / kg IV
Fosphenytoin 20 mg PE/ kg IV
30-40 min
Blood Cultures, ABG
AED # 2
Phenytoin, Phenobarbital or Fosphenytoin
20 mg / kg IV
Intubation
? Antiobiotics
50-60 min
?CT, ?LP
Admit to ICU
Airway control
Circulatory, fluid and metabolic support
Seizure longer than 60 min
EEG Monitoring
Pharmacologic Coma
  • Benzodiazepine-midazolam
  • Pentobarbitol
  • Propofol

Pharmacologic Coma for Refractory Status Epilepticus

Drug Loading Dose Maintenance Dose Comments
pentobarbital
(Children)
15 mg/kg iv over 1 hour
5 mg/kg q 20 minutes
0.5 - 1.0 mg/kg/hr
after 12 - 24 hrs seizure free
Decrease dose by 50%
pentobarbital
(Adults)
5-12 mg/kg iv over 1 hour
5 mg/kg q 20 minutes
1 - 10 mg/kg/hr titrated to burst suppression
after 12 - 24 hrs seizure free
Decrease dose by 50%
(Bleck,1999)
midazolam
(Children)
150 - 200 µg/kg iv
1 - 10 µg/kg/minute
mean drip rate 2.3 µg/kg/minute
(Rivera et al., 1993)
midazolam
(Adults)
0.2 mg/kg iv
0.1 - 0.2 mg/kg/hr
mean drip rate 2.3 µg/kg/minute
(Kumar and Bleck,1992)
propofol
(Adults)
3-5 mg/kg iv
1 - 15 mg/kg/hr titrated to burst suppression
(Stecker, et. al., 1998)
Rapid infusion may induce withdrawal "seizures"
(Finley, et. al. 1993) (Walder et.al., 2002)

Status Epilepticus Evaluation - Treatment Reminders

  • Ventilation is to be anticipated. Use of AEDs to stop seizures and respiration for intubation is better than giving neuromuscular blockade alone.
  • Most easily missed diagnosis of causes of status epilepticus
    • Bacterial meningitis
    • Encephalitis
    • Abuse/unsuspected trauma
    • Drug ingestion
  • Lumbar Puncture should be performed in most cases
    • All cases of status epilepticus and fever
    • Only after the the patient is stabilized
    • Unlessspecific contraindication to LP exist
  • Contraindications to LP
    • Skin infection at LP site
    • Cardiovascular instability
    • Signs of Increased Intracranial Pressure
      • Papilledema
      • Herniation
      • Posturing
    • Coaggulopathy
  • Neuro-Imaging
    • CT Scan may be necessary:
      • To evaluate safety of LP
      • To rule out hemorrhage or large mass lesion
    • MRI will almost always be performed later, even if CT is normal.
  • Use correct and adequate Anti-seizure drug doses. Epileptics and non-epileptics in status require the same drug doses. Remember, outcome is determined by etiology, age, duration and treatment. You can affect only the treatment.

Status Epilepticus Summary

Status epilepticus is a common and serious condition. Children are more Susceptible to the occurrence of status, but more resistant to injury. Normal children and children with febrile status have a favorable prognosis. In all respects, children with prior, new or progressive CNS injury are more prone to have refractory status epilepticus. As a group they have higher morbidity and mortality, including later epilepsy, recurrent status, and the need for prolonged anti-epileptic drug therapy.

Improved outcome is a result of timely and appropriate evaluation and treatment.