Drislane FW. Convulsive status epilepticus in adults: Treatment and prognosis. UpToDate. Updated November 12, 2020. https://www.uptodate.com/contents/convulsive-status-epilepticus-in-adults-treatment-and-prognosis
Wylie T, Sandhu DS, Goyal A, Murr N. Status Epilepticus. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2020 Jan–. Updated 2020 September 25, 2020. Accessed November 1, 2020. PMID: 28613459.
Helman A, Koblic P, Reid A, Kovacs G. Emergency Management of Status Epilepticus. Emergency Medicine Cases. Published December 2019. Accessed November 1, 2020. https://emergencymedicinecases.com/status-epilepticus
Kapur J, Elm J, Chamberlain JM, et al; NETT and PECARN Investigators. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus. N Engl J Med. 2019 Nov 28;381(22):2103-2113. doi: 10.1056/NEJMoa1905795. PMID: 31774955; PMCID: PMC7098487.
Morgenstern J. Status Epilepticus: Emergency Management. First10EM. Published June 3, 2019. Accessed November 1, 2020. https://first10em.com/status-epilepticus-update/
Treiman DM, Meyers PD, Walton NY, et al. A comparison of four treatments for generalized convulsive status epilepticus. Veterans Affairs Status Epilepticus Cooperative Study Group. N Engl J Med. 1998 Sep 17;339(12):792-8. doi: 10.1056/NEJM199809173391202. PMID: 9738086.
Definition and EtiologyTop
Status epilepticus (SE) is a neurologic emergency warranting rapid recognition and treatment due to the associated high rates of morbidity and mortality. SE has been defined as:
1) >5 minutes of clinical or electroencephalographic (EEG) seizure activity; or
2) ≥2 recurrent seizures without recovery to baseline.
Refractory SE is an SE that persists after fist-line and second-line treatment. Super-refractory SE is defined as an SE that continues for ≥24 hours after the use of anesthetic therapy, including cases that recur when weaning off the anesthetic agent.
The etiology of SE is variable and heterogenous. Although it may occur as an episode in a patient with established epilepsy, SE often represents an acute central nervous system (CNS) illness.
Important causes of SE: (some of them are reversible): CNS infections and other acute infections, cerebrovascular disease, brain trauma, hypertensive crisis/posterior reversible encephalopathy syndrome (PRES), other causes of raised intracranial pressure (ICP), autoimmune disorder, metabolic disorder (eg, hyponatremia), drug toxicity and drug withdrawal (including alcohol), preexisting epilepsy (spontaneous or triggered SE). Always check for possible pregnancy (eclampsia).
There are different types of SE:
1) Grand mal SE (tonic-clonic SE): A non–self-limiting grand mal or a series of repetitive grand mals without recovery.
2) Focal SE: For example, ongoing motor Jacksonian activity or other focal seizure activity. A special form of focal motor SE is called “epilepsia partialis continua.”
3) Nonconvulsive SE (NCSE): SE without overt ictal motor symptoms. NCSE does not designate a single entity but is used to refer to several various conditions. Major forms:
a) SE of complex partial seizures.
b) SE of absences (spike-wave status).
c) Subtle status as a consequence of an ongoing major SE after treatment.
4) Other: For instance, status myoclonicus.
NCSE is an important SE variant to be considered in intensive care units and in patients with any neurologic or neuropsychiatric symptoms that are otherwise unexplained.
Diagnosis and ManagementTop
A diagnosis of SE is made clinically in many instances, particularly in patients with tonic-clonic SE and those with forms of obvious focal SE. In other situations, the diagnosis of SE is based on EEG aimed at detecting ictal activity in patients with nonobvious or puzzling symptoms or after a seemingly terminated SE. If the patient is said to have a seizure and the seizure is still active when the patient is examined by a physician, it is likely an SE.
The following steps should be considered rapidly and simultaneously to recognize the possible reversible causes and to prepare for early therapeutic intervention:
1) Establish a team. Call for help as necessary.
2) Establish vital signs monitoring, including temperature and oxygenation.
3) Prepare to support ventilation, oxygenation, and blood pressure, as all these may be compromised by treatment (oxygen supply and delivery, ventilation equipment, infusion of fluids and vasopressors as required). Place the patient in a lateral position, administer oxygen, and apply suction, as necessary. Establish IV accesses. Start pharmacologic treatment within 5 minutes (see Treatment, below). Monitor temperature.
4) Laboratory tests:
a) Rapid measurement of the glucose level (hypoglycemia must not be missed).
b) A broad range of tests, including electrolytes (sodium, calcium, magnesium), renal and liver function tests, and cell count. Consider creatine kinase (CK), myoglobin, and lactate levels.
c) Toxicology studies as appropriate.
d) Evaluation of antiseizure drug levels, if applicable.
5) Imaging studies as necessary and possible: Computed tomography (CT) in most cases; magnetic resonance imaging (MRI) can be considered at later stages.
6) Cerebrospinal fluid (CSF) analysis: When needed (suspected CNS infection), this should be performed as soon as feasible.
7) EEG: This should be performed whenever available, particularly to exclude or detect ongoing ictal activity (especially in patients who do not recover as expected).
An important differential diagnosis in a scenario of presumed motor SE is the prolonged psychogenic nonepileptic seizure (PNES) (see Seizures and Epilepsy) or “dissociative status,” which is best recognized by an experienced professional observer. In such patients the goal is to avoid most invasive procedures.
Pharmacologic termination of SE as soon as possible is the major aim of SE therapy. The longer the SE lasts, the worse the chance of successful termination and good outcome. Early institution of therapy improves the chances of successful SE resolution. Delayed interventions and insufficient drug dosage are the main threats to treatment success. Any institution shall aim for establishing a clear in-house SE management algorithm to be followed.
1. First-line treatment: Benzodiazepines (to be started within 5 minutes). Check which drugs and in what doses have already been given (eg, by ambulance staff).
1) IV lorazepam (0.1 mg/kg bolus; max, 4 mg). The initial 4 mg in patients with grand mal SE can be followed by another 4 mg or by 2 mg administered twice.
2) IM midazolam 10 mg (if IV access cannot be established; dose for a patient weighing >40 kg).
3) Alternatives: IV diazepam (0.15-0.2 mg/kg; max, 10 mg), buccal midazolam.
Start a classic antiseizure drug even if the first-line benzodiazepines effectively stop the SE.
2. Second-line treatment: Classic antiseizure drugs (to be started within 10-15 minutes): Consider IV phenytoin or valproic acid, or alternatives (eg, levetiracetam).
1) IV levetiracetam (60 mg/kg; max, 4500 mg) is well tolerated. It should be preferably administered over ≥15 minutes.
2) IV valproic acid (10-20 mg/kg as initial bolus in 5-10 min followed by 6 mg/kg/h; max, 3000 mg) is most often well tolerated. However, susceptible patients can develop acute encephalopathy, liver toxicity, or both.
3) IV phenytoin (20 mg/kg at 25-50 mg/min; max, 1500 mg) requires cardiovascular monitoring and a safe IV line, preferably through a central line (extravascular administration is hazardously tissue toxic and may lead to purple glove syndrome). Administer the drug only in normal saline solution. Phenytoin should be avoided if the patient was already receiving this agent, if the SE is due to toxic causes, or if the patient is at high cardiovascular risk.
3. Third-line treatment (refractory SE): Consider IV anesthetics: Propofol is usually preferred. Alternatives include midazolam and phenobarbital.
1) IV propofol: The usual dose is IV bolus 2 mg/kg followed by 3 to 5 (max 10) mg/kg/h. IV administration is limited in dosage and time because of the risk of propofol infusion syndrome.
2) IV midazolam: The usual dose is IV bolus of 0.2 mg/kg followed by 0.1 to 0.5 mg/kg/h (in refractory SE the dose may be higher, up to 2 mg/kg/h).
3) IV phenobarbital: The usual dose is 15 to 20 mg/kg given at 50 mg/min.
4) Additional further options: Other barbiturates, volatile anesthetics, ketamine.
In special individual scenarios the following options have been tried and could be discussed: other antiseizure drugs (eg, lacosamide), magnesium (eclampsia), acute neurosurgery, electroconvulsive therapy.