Status Epilepticus - An Overview of Management and Treatment

The definition of status epilepticus has changed over time. Historically, generalized convulsive status epilepticus (GCSE) was defined as one seizure greater than 30 minutes or multiple seizures where baseline patient function is not regained within a 30 minute time span. [1]

Regardless, because of the increase in mortality as seizures continues, it is recommended that treatment be started once seizures have continued after a few minutes.

An appropriate definition for status epilepticus in an emergent setting, in order to prevent refracture status epilepticus and to decrease morbidity from adverse events such as cardiovascular collapse is [2-4]:

• Seizure lasting ? 5 minutes or,

• ? 2  seizures in which patient does not return to baseline mental status

The mortality rate for adults with a first time presentation of (GCSE) is high, approximately 20 percent [12-13].

Initial Assessment

• Airway, Breathing and Circulation Assessment

  • Is the patient breathing and protecting their airway?

  • Obtain IV access

    • Laboratory studies should be sent including a comprehensive metabolic panel including magnesium and phosphorous, complete blood count and differential, toxicology screens, anticonvulsant level (if patient is known to be taking an anticonvulsant)

• Fingerstick glucose

• Focused Medical History

• Rapid Neurological Assessment

First-line Therapy

Benzodiazepines are the first-line medications for patients in GCSE, typically followed by anticonvulsant medications to prevent recurrence. Some common benzodiazepines include:

• Lorezepam - use as first-line benzodiazepine for GCSE has been supported by studies done by Veteran Affairs [3].

  • Weight based dosing: 0.1mg/kg or,

  • 4 mg fixed dose

  • Reassessment after 1 minute and readminister as needed if seizures continue.

• Diazepam

  • 0.15 mg/kg IV, up to 10 mg per dose

• Midazolam – A rapidly acting benzodiazepine with a short half-life. Ideal medication to be used as first line if patient does not already have an IV since it can be given intramuscularly. Can also be used as a continuous infusion in the management of refractory status epilepticus.

There is no maximum dose of benzodiazepine to be given in GCSE, however the clinician should be aware of the medication’s clinical effect such as adverse effects on blood pressure, respiratory status and it’s efficacy on seizure control.

Second Line: Urgent Control Therapy

Typically this is done with the use of anticonvulsant medications. Levetiracetam as the first-line anticonvulsant in benzodiazepine refractory status epilepticus has been supported in multiple observational studies [5-11]. Dosing has been suggested to be between 1000 to 3000 mg IV in adults [1]. A meta-analysis shows efficacy for the use of levetiracetam to be 68 percent in benzodiazepine refractory status epilepticus [11].

Other control therapies include:

• Phenytoin or Fosphenytoin

• Valproic acid

Refractory Status Epilepticus

Defined as ongoing seizures despite appropriate treatment with benzodiazepine and anticonvulsant medications. Approximately 20% of patients presenting with GCSE will progress to refractory status epilepticus. The medications to be considered are typically given as an initial bolus followed by an infusion, they are [14]:

• Midazolam

• Propofol

• Pentobarbital

Pentobarbital was shown to be more effective than propofol or midazolam in preventing breakthrough seizures however it was associated with increased risk of hypotension. Although the risk of death did not differ from choice of drug selection in patients with refractory status epilepticus [15].

For patients in refractory status epilepticus who requirement continuous infusions of either midazolam, propofol or pentobarbital, intubation is often required given the degree of sedation and depression in respiratory status caused by these medications.

References

1. Guidelines for epidemiologic studies on epilepsy. Commission on Epidemiology and Prognosis, International League Against Epilepsy. Epilepsia 1993; 34:592.

2. Lowenstein DH, Bleck T, Macdonald RL. It's time to revise the definition of status epilepticus. Epilepsia 1999; 40:120.

3. Brophy GM, Bell R, Claassen J, et al. Guidelines for the evaluation and management of status epilepticus. Neurocrit Care 2012; 17:3.

4. Chen JW, Wasterlain CG. Status epilepticus: pathophysiology and management in adults. Lancet Neurol 2006; 5:246.

5. Knake S, Gruener J, Hattemer K, et al. Intravenous levetiracetam in the treatment of benzodiazepine refractory status epilepticus. J Neurol Neurosurg Psychiatry 2008; 79:588.

6. Möddel G, Bunten S, Dobis C, et al. Intravenous levetiracetam: a new treatment alternative for refractory status epilepticus. J Neurol Neurosurg Psychiatry 2009; 80:689.

7. Eue S, Grumbt M, Müller M, Schulze A. Two years of experience in the treatment of status epilepticus with intravenous levetiracetam. Epilepsy Behav 2009; 15:467.

8. Swisher CB, Doreswamy M, Gingrich KJ, et al. Phenytoin, levetiracetam, and pregabalin in the acute management of refractory status epilepticus in patients with brain tumors. Neurocrit Care 2012; 16:109.

9. Berning S, Boesebeck F, van Baalen A, Kellinghaus C. Intravenous levetiracetam as treatment for status epilepticus. J Neurol 2009; 256:1634.

10. Uges JW, van Huizen MD, Engelsman J, et al. Safety and pharmacokinetics of intravenous levetiracetam infusion as add-on in status epilepticus. Epilepsia 2009; 50:415.

11. Yasiry Z, Shorvon SD. The relative effectiveness of five antiepileptic drugs in treatment of benzodiazepine-resistant convulsive status epilepticus: a meta-analysis of published studies. Seizure 2014; 23:167.

12. DeLorenzo RJ, Pellock JM, Towne AR, Boggs JG. Epidemiology of status epilepticus. J Clin Neurophysiol 1995; 12:316.

13. Logroscino G, Hesdorffer DC, Cascino G, et al. Short-term mortality after a first episode of status epilepticus. Epilepsia 1997; 38:1344.

14. Claassen J, Hirsch LJ, Emerson RG, Mayer SA. Treatment of refractory status epilepticus with pentobarbital, propofol, or midazolam: a systematic review. Epilepsia 2002; 43:146.

15. Rossetti AO, Logroscino G, Bromfield EB. Refractory status epilepticus: effect of treatment aggressiveness on prognosis. Arch Neurol 2005; 62:1698.