Status epilepticus: Difference between revisions

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==Overview==
==Background==
*Seizures are abnormal neuronal activity with various neurological sequale.
*Continuous seizure activity lasting >5 minutes, or ≥2 seizures without return to baseline<ref name="trinka">Trinka E, et al. A definition and classification of status epilepticus. Report of the ILAE Task Force. ''Epilepsia''. 2015;56(10):1515-1523. PMID 26336950.</ref>
**Further defined by whether they involve 1 hemisphere (partial) or both hemispheres (generalized). While generalized seizures surely cause an alteration in mental status, seizures involving one hemisphere (partial) may further be subdivided by whether they maintain baseline mental status (simple) or an alteration (complex).  
*'''Time-sensitive emergency''' — mortality increases with duration of seizure
*Epilepsy is defined a 2 or more epileptic seizures that occur unprovoked by any identifiable cause. This include all seizure events with the exception of febrile or neonatal seizures.  
*30-day mortality: 20% overall; higher in elderly and those with anoxic injury
**Further subclassified into cryptogenic (meaning unknown cause) or symptomatic (meaning associated with previous CNS insult).  
*Refractory SE: seizures persisting despite two appropriate first-line agents
***Symptomatic seizures further subdefined as acute or remote (depending on if > or < 1 week after CNS insult)
*Super-refractory SE: seizures persisting >24 hours despite anesthetic agents
*Status epilepticus is the persistence of seizure beyond 30 minutes. (includes either persistent clinical seizure activity OR  no return to consciousness during that timeframe or between attacks.
**Functionally presume people to be in status if clinically seizing beyond 5 minutes
**Status Epilepticus can be defined as “convulsive” (meaning obvious clinical signs of seizure activity –tonic clonic/myoclonic/tonic) or “Nonconsulsive” meaning no obvious signs of activity but decreased level of consciousness.
***NCSE (Non consulsive status) is a critical and relevant consideration. Up to 50% of patients with generalized tonic-clonic seizures will have NCSE after convulsions have subsided.
*Seizure  type and associated EEG findings are at core of determining risk of recurrence and indication for antiepileptic therapy. Follow the “seizure” link (pending Jan 2014) for more information on the non-acute general treatment of seizures.


===Management of acute status epilepticus===
==Etiology==
Overview
*Anti-epileptic drug (AED) non-compliance or subtherapeutic levels (most common in known epileptics)
*The general theme of seizure treatment  is to
*Acute CNS injury: [[Stroke (main)|stroke]], [[Traumatic brain injury|TBI]], [[Meningitis|CNS infection]], tumor
#Address immediate concerns (ABC’s) (primarily referring to airway/breathing)  
*Metabolic: [[Hypoglycemia|hypoglycemia]], [[Hyponatremia|hyponatremia]], [[Hypocalcemia|hypocalcemia]], hepatic failure, uremia
##Constantly return to evaluate this for the duration of seizure episode
*Toxicologic: [[Ethanol withdrawal|alcohol withdrawal]], [[Benzodiazepine withdrawal]], [[Isoniazid toxicity|INH]], [[Organophosphate toxicity|organophosphates]], [[Cocaine toxicity|cocaine]], [[Tricyclic antidepressant toxicity|TCA]]
###continuously monitor O2 saturations  via pulse oximetry
*[[Eclampsia]] (pregnant/postpartum patients)
###periodic blood gases to evaluate for CO2 retention and lactic acidosis (q10-15mins- up to clinical judgement).
*Febrile status epilepticus in children
#Manage the seizure activity with medications along with investigation/correction of causes.
 
##Treat quickly; Do not hold medications. Treatment initiated in first 30 minutes has 80% response. Drops to 40% around two hours
==Clinical Features==
###Medication regimes include a benzodiazepine to terminate seizure in immediate term and an anti-epileptic drug (AED) to continue longer term neuronal suppression.  Continued seizure activity is treated by additive AED’s and/or sedating medications.
*Generalized convulsive SE: continuous tonic-clonic activity, most readily recognized
###Very often phenytoin is used for AED (Cost and plethora of studies) however alternatives exist Leveteriacetam, lacosamide, valproate with lesser side effect profile. You may refer to pharmacy for assistance with typical protocol, otherwise phenytoin is acceptable and can always be changed to another AED later.
*Non-convulsive SE: subtle or no motor manifestations; persistent altered mental status
====Take a Stepwise Approach: Timeline====
**Must maintain high suspicion in patients who remain altered after apparent seizure cessation
# 0-5 minutes
*Complications: [[Rhabdomyolysis|rhabdomyolysis]], [[Hyperthermia|hyperthermia]], lactic acidosis, aspiration, neuronal injury
##Is this patient still seizing ? (look for return of consciousness) or if on EEG look to EEG (Reading EEGs link to come).
 
###If this is first episode, may await seizure to break however ready materials to be given should seizure persist greater than 5 minutes
==Differential Diagnosis==
##Obtain Diagnostic  labs (CBC, CEM 10, LFT, coagulation, AED levels (If indicated: assess if therapeutic), ECG, troponins, toxicology screen, pregnancy test (preparation for possible CT), blood gas, continuous SaO2, BP and continuous ECG.
{{Seizure DDX}}
##Ready medications to be given if seizure persists > 5 minutes
 
###lorazepam (0.1mg/kg max given in 2-4 mg aliquots )
==Evaluation==
### AED loading agent  (Fosphenytoin 20mg/kg)
*'''Bedside glucose''' — immediately
### Thiamine 100mg IV along with 50ml D50IV.
*Labs: BMP (Na, Ca, Mg, glucose), CBC, AED levels, lactate, VBG, LFTs, toxicology screen
##Briefly familiarize patient H+P to help guide diagnostic causes
*CT head — once stabilized; evaluate for structural cause
###PMHx: Sz History? (get AED levels/home dosages), CNS insults?
*Continuous EEG — if available; essential to diagnose non-convulsive SE
####description of previous seizures semiology (if applicable) – jerking/automatisms/gaze deviation
*LP if infection suspected (after CT and when safe)
###Medications: anything that reduces seizure threshold?
*CK, urinalysis (myoglobinuria) if prolonged seizure
###Physical Exam: Neuro evaluation
 
####while in convulsive status patient is obviously seizing and one should continue timeline for acute treatment. The neuro exam is primarily focused on identifying 1. Neuro signs to help localize seizure focus 2.identifying NCSE; focusing on recognizing an improvement of wakefulness/mental status.
==Management==
#####No improvement in wakefulness >20 minutes or continued AMS > 30-60 minutes prompts concern for NCSE and requires 24-48hr cEEG
===Time 0-5 min: Stabilize===
#6-10 minutes (seizure persists)
*ABCs, supplemental O2, cardiac monitor, IV access
##Administer thiamine 100mg IV along with 50ml D50IV (empirically for possible hypoglycemia)
*'''Glucose''': check immediately; give '''D50W 50 mL IV''' (or D10W) if hypoglycemic
###May forego if hypoglycemia ruled out with recent CEM panel.
*Thiamine 100 mg IV before glucose if malnourished or alcoholic
##Administer the 2-4mg lorazepam aliquot over 2 minutes.
*Position patient to prevent aspiration; suction as needed
###Repeat 1x (max dose 0.1mg/kg) if seizure continues another 5 minutes.
 
###If no IV access available. Diazepam may be given rectally (20mg PR) or Midazolam (10mg intrabucally/intranasally).
===Time 5-20 min: First-Line — Benzodiazepines===
#10-20 minutes
*'''[[Lorazepam]]''' 0.1 mg/kg IV (max 4 mg/dose), may repeat x1 in 5 min<ref name="silber">Silbergleit R, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. ''N Engl J Med''. 2012;366(7):591-600. PMID 22335736.</ref>
##Admin AED loading agent (Fosphenytoin 20mg/kg). MAX INFUSION RATE 150mg/min
*If no IV access: [[Midazolam]] 10 mg IM (most effective prehospital per RAMPART trial)
###Phenytoin associated with hypotension. Fosphenytoin use attenuates some of this risk however still significant. Administer with frequent BP checks and ECG monitoring.  
*Alternatives: [[Diazepam]] 0.2 mg/kg IV (max 10 mg), or diazepam 20 mg PR
###Continue AED maintenance with target phenytoin level 2-3 G/mL
 
##If seizure persists may rebolus 1x with additional Fosphenyoitn 10mg/kg bolus.
===Time 20-40 min: Second-Line — Anti-Epileptic Drug===
##OTHER OPTION
*'''[[Levetiracetam]]''' 60 mg/kg IV (max 4500 mg) over 15 min<ref name="kapur">Kapur J, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus (ESETT). ''N Engl J Med''. 2019;381(22):2103-2113. PMID 31774955.</ref>
###if patient on AED at home, may reload with home medication: Some examples below
*[[Fosphenytoin]] 20 mg PE/kg IV (max rate 150 mg PE/min)
##IV valproate: 20mg/kg over 10 minutes. May re bolus (same dose) 1x if seizure persists > 5 minutes following
*[[Valproic acid]] 40 mg/kg IV (max 3000 mg) over 10 min
##IV keppra 1000-4000mg IV
*ESETT trial: all three equally effective (~50% success each)
##Reassess ABC status
 
##Make arrangements for possible ICU transfer ( If applicable - as next step is intubation).
===Time >40 min: Refractory SE===
#20-60 minutes - If still seizing despite 2 drug interventionconsidered refractory status epilepticus
*'''[[Intubation (main)|Intubation]]''' and continuous infusion of anesthetic agent:
##Intubate for airway protection (As we will definitively sedate to the point of respiratory compromise)  
**[[Midazolam]] 0.2 mg/kg IV bolus, then 0.1-2 mg/kg/hr
##Place arterial line (Continuous BP monitoring with propofol infusion)
**[[Propofol]] 2 mg/kg IV bolus, then 2-10 mg/kg/hr (monitor for propofol infusion syndrome)
##Medications (May use propofol as pressure tolerates, otherwise midazolam; Typically start with propofol since may regain neuro exam faster, and add midazolam).
**[[Pentobarbital]] 5 mg/kg IV bolus, then 1-5 mg/kg/hr
###IV propofol (causes hypotension)
*Continuous EEG monitoring required
#### 1mg/kg bolus with continued boluses (same dose) every 3-5 minutes until seizures stop (As BP tolerates).  
*Target: burst-suppression for 24-48 hours
####May place on cIV infusion 1-15 mg/kg/h (Do not exceed >5mg/kg/h in 24 hrs)
 
###IV midazolam (less hypotension, longer sedation than propofol)
===Special Situations===
####0.2mg/kg bolus with repeat boluses  (Same dose) every 5 minutes until seizures stop (max dose 2mg/kg)
*[[Isoniazid toxicity|INH overdose]]: Pyridoxine (B6) gram-for-gram (empiric 5 g IV if dose unknown)
####May place on cIV 0.05-2.0 mg/kg/h (up to 200mg/h for 70kg patient).
*[[Eclampsia]]: Magnesium sulfate 4-6 g IV
#> 60 minutes
*[[Hyponatremia]]: Hypertonic saline (3%) 100 mL IV bolus
##Place in pentobarbital coma
 
###5 mg/kg up to 50mg/min. Repeat boluses (same dose) until seizure stop.
==Disposition==
###cIV 1mg/kg/h  titrated to suppression on cEEG.
*ICU admission for all SE patients
*Neurology consultation
*Patients with rapidly terminated seizures who return to baseline may be managed on a monitored floor
 
==See Also==
*[[Seizure]]
*[[First-time seizure]]
*[[Eclampsia]]
*[[Febrile seizure]]
*[[Ethanol withdrawal]]
 
==References==
<references/>
 
[[Category:Neurology]]

Latest revision as of 09:23, 22 March 2026

Background

  • Continuous seizure activity lasting >5 minutes, or ≥2 seizures without return to baseline[1]
  • Time-sensitive emergency — mortality increases with duration of seizure
  • 30-day mortality: 20% overall; higher in elderly and those with anoxic injury
  • Refractory SE: seizures persisting despite two appropriate first-line agents
  • Super-refractory SE: seizures persisting >24 hours despite anesthetic agents

Etiology

Clinical Features

  • Generalized convulsive SE: continuous tonic-clonic activity, most readily recognized
  • Non-convulsive SE: subtle or no motor manifestations; persistent altered mental status
    • Must maintain high suspicion in patients who remain altered after apparent seizure cessation
  • Complications: rhabdomyolysis, hyperthermia, lactic acidosis, aspiration, neuronal injury

Differential Diagnosis

Seizure

Evaluation

  • Bedside glucose — immediately
  • Labs: BMP (Na, Ca, Mg, glucose), CBC, AED levels, lactate, VBG, LFTs, toxicology screen
  • CT head — once stabilized; evaluate for structural cause
  • Continuous EEG — if available; essential to diagnose non-convulsive SE
  • LP if infection suspected (after CT and when safe)
  • CK, urinalysis (myoglobinuria) if prolonged seizure

Management

Time 0-5 min: Stabilize

  • ABCs, supplemental O2, cardiac monitor, IV access
  • Glucose: check immediately; give D50W 50 mL IV (or D10W) if hypoglycemic
  • Thiamine 100 mg IV before glucose if malnourished or alcoholic
  • Position patient to prevent aspiration; suction as needed

Time 5-20 min: First-Line — Benzodiazepines

  • Lorazepam 0.1 mg/kg IV (max 4 mg/dose), may repeat x1 in 5 min[2]
  • If no IV access: Midazolam 10 mg IM (most effective prehospital per RAMPART trial)
  • Alternatives: Diazepam 0.2 mg/kg IV (max 10 mg), or diazepam 20 mg PR

Time 20-40 min: Second-Line — Anti-Epileptic Drug

  • Levetiracetam 60 mg/kg IV (max 4500 mg) over 15 min[3]
  • Fosphenytoin 20 mg PE/kg IV (max rate 150 mg PE/min)
  • Valproic acid 40 mg/kg IV (max 3000 mg) over 10 min
  • ESETT trial: all three equally effective (~50% success each)

Time >40 min: Refractory SE

  • Intubation and continuous infusion of anesthetic agent:
    • Midazolam 0.2 mg/kg IV bolus, then 0.1-2 mg/kg/hr
    • Propofol 2 mg/kg IV bolus, then 2-10 mg/kg/hr (monitor for propofol infusion syndrome)
    • Pentobarbital 5 mg/kg IV bolus, then 1-5 mg/kg/hr
  • Continuous EEG monitoring required
  • Target: burst-suppression for 24-48 hours

Special Situations

  • INH overdose: Pyridoxine (B6) gram-for-gram (empiric 5 g IV if dose unknown)
  • Eclampsia: Magnesium sulfate 4-6 g IV
  • Hyponatremia: Hypertonic saline (3%) 100 mL IV bolus

Disposition

  • ICU admission for all SE patients
  • Neurology consultation
  • Patients with rapidly terminated seizures who return to baseline may be managed on a monitored floor

See Also

References

  1. ↑ Trinka E, et al. A definition and classification of status epilepticus. Report of the ILAE Task Force. Epilepsia. 2015;56(10):1515-1523. PMID 26336950.
  2. ↑ Silbergleit R, et al. Intramuscular versus intravenous therapy for prehospital status epilepticus. N Engl J Med. 2012;366(7):591-600. PMID 22335736.
  3. ↑ Kapur J, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus (ESETT). N Engl J Med. 2019;381(22):2103-2113. PMID 31774955.
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