Status epilepticus: Difference between revisions
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==Background==
==Background==
===Definition===
*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>
*Status epilepticus is the persistence of seizure beyond 20 minutes. <ref>Brodie MJ Status epilepticus in adults. Lancet. 1990 Sep 1; 336(8714):551-2.</ref>
*'''Time-sensitive emergency''' — mortality increases with duration of seizure
**Functionally presume people to be in status if clinically seizing beyond 5 minutes<ref>Lowenstein DH, Alldredge BK.  Status epilepticus.  N Engl J Med. 1998; 338:970-976</ref>
*30-day mortality: 20% overall; higher in elderly and those with anoxic injury
***Convulsive - meaning obvious clinical signs of seizure activity –tonic clonic/myoclonic/tonic
*Refractory SE: seizures persisting despite two appropriate first-line agents
***Non-convulsive - meaning no obvious signs of activity but decreased level of consciousness
*Super-refractory SE: seizures persisting >24 hours despite anesthetic agents
**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.


 
==Etiology==
*Seizures are abnormal neuronal activity with various neurological sequale.
*Anti-epileptic drug (AED) non-compliance or subtherapeutic levels (most common in known epileptics)
**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).
*Acute CNS injury: [[Stroke (main)|stroke]], [[Traumatic brain injury|TBI]], [[Meningitis|CNS infection]], tumor
*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.
*Metabolic: [[Hypoglycemia|hypoglycemia]], [[Hyponatremia|hyponatremia]], [[Hypocalcemia|hypocalcemia]], hepatic failure, uremia
**Further subclassified into cryptogenic (meaning unknown cause) or symptomatic (meaning associated with previous CNS insult).
*Toxicologic: [[Ethanol withdrawal|alcohol withdrawal]], [[Benzodiazepine withdrawal]], [[Isoniazid toxicity|INH]], [[Organophosphate toxicity|organophosphates]], [[Cocaine toxicity|cocaine]], [[Tricyclic antidepressant toxicity|TCA]]
***Symptomatic seizures further subdefined as acute or remote (depending on if > or < 1 week after CNS insult)
*[[Eclampsia]] (pregnant/postpartum patients)
 
*Febrile status epilepticus in children
*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.


==Clinical Features==
==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|rhabdomyolysis]], [[Hyperthermia|hyperthermia]], lactic acidosis, aspiration, neuronal injury


==Differential Diagnosis==
==Differential Diagnosis==
{{Seizure DDX}}
{{Seizure DDX}}


==Diagnosis==
==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


==ED Management==
==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


==Neuro ICU Management==
===Time 5-20 min: First-Line — Benzodiazepines===
*Address immediate concerns (ABC’s) (primarily referring to airway/breathing)
*'''[[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>
**Constantly return to evaluate this for the duration of seizure episode
*If no IV access: [[Midazolam]] 10 mg IM (most effective prehospital per RAMPART trial)
***continuously monitor O2 saturations  via pulse oximetry
*Alternatives: [[Diazepam]] 0.2 mg/kg IV (max 10 mg), or diazepam 20 mg PR
***periodic blood gases to evaluate for CO2 retention and lactic acidosis (q10-15mins- up to clinical judgement).
*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
***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.
***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.
*Consider anesthesia consult for possible inhaled anesthetics (isoflurane, desflurane) in OR room for refractory status epilepticus (RSE)
**RSE = continued seizures after 2 - 3 antiepileptic drugs have failed
**Research suggests inhaled isoflurane/desflurane are well tolerated<Mirsattari SM et al. Treatment of refractory status epilepticus with inhalational anesthetic agents isoflurane and desflurane. Arch Neurol. 2004 Aug;61(8):1254-9.</ref>
===Take a Stepwise Approach: Timeline===
====0-5 minutes====
*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
*Protect patient
**turn on side prn for airway protection if vomitting to attenuate aspiration events. Remove any obvious dangerous material that may hurt the patient.
**DO NOT, try to limit patient movement by holding extremities down. DO NOT place bite block (risk of occluding airway).
*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.
*Ready medications to be given if seizure persists > 5 minutes
**lorazepam (0.1mg/kg max given in 2-4 mg aliquots )
** AED loading agent  (Fosphenytoin 20 PE/kg, at 150 mg/min)
***PE = phenytoin equivalents (1.5 mg fosphenytoin = 1 mg phenytoin)
***20 mg/kg phenytoin is given slower at 50 mg/min
** Thiamine 100mg IV along with 50ml D50IV
** Consider 5 g of pyridoxine (Vitamin B6) over 5-10 min, repeat up to total 20 g, for TB patients with suspected INH toxicity (urban hospital, especially in international medicine)<ref>Weisiger RA. Isoniazid Toxicity Treatment and Management - Supportive and Pharmacologic Therapy. Updated Dec 16, 2014. http://emedicine.medscape.com/article/180554-treatment*d8</ref><ref>Vasu T and Saluja J. INH Induced Status Epilepticus: Response to Pyridoxine. Indian J Chest Dis Allied Sci 2006; 48: 205-206.</ref>
*Briefly familiarize patient H+P to help guide diagnostic causes
**PMHx: Sz History? (get AED levels/home dosages), CNS insults?
***description of previous seizures semiology (if applicable) – jerking/automatisms/gaze deviation
**Medications: anything that reduces seizure threshold?
**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.
****No improvement in wakefulness >20 minutes or continued AMS > 30-60 minutes prompts concern for NCSE and requires 24-48hr cEEG


====6-10 minutes (seizure persists)====
===Time 20-40 min: Second-Line — Anti-Epileptic Drug===
*Administer thiamine 100mg IV along with 50ml D50IV (empirically for possible hypoglycemia)
*'''[[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>
**May forego if hypoglycemia ruled out with recent CEM panel.
*[[Fosphenytoin]] 20 mg PE/kg IV (max rate 150 mg PE/min)
*Administer the 2-4mg lorazepam aliquot over 2 minutes.  
*[[Valproic acid]] 40 mg/kg IV (max 3000 mg) over 10 min
**Repeat 1x (max dose 0.1mg/kg) if seizure continues another 5 minutes.
*ESETT trial: all three equally effective (~50% success each)
**If no IV access available. Diazepam may be given rectally (20mg PR) or Midazolam (10mg intrabucally/intranasally).
====10-20 minutes ====
*Admin AED loading agent (Fosphenytoin 20 PE/kg). MAX INFUSION RATE 150mg/min
**Phenytoin associated with hypotension. Fosphenytoin use attenuates some of this risk however still significant. Administer with frequent BP checks and ECG monitoring.
***Continue AED maintenance with target phenytoin level 2-3 G/mL after seizure subsides (typically qd checks). Defer to neurology for long term AED management.
**If seizure persists may rebolus 1x with additional Fosphenyoitn 10 PE/kg bolus.
*OTHER OPTION
**if patient on AED at home, may reload with home medication: Some examples below
***IV valproate: 20mg/kg over 10 minutes. May re bolus (same dose) 1x if seizure persists > 5 minutes following
***IV keppra 1000-4000mg IV
*Reassess ABC status
*Make arrangements for possible ICU transfer ( If applicable - as next step is intubation).


====20-60 minutes (refractory status epilepticus)====
===Time >40 min: Refractory SE===
*Intubate for airway protection (As we will definitively sedate to the point of respiratory compromise)
*'''[[Intubation (main)|Intubation]]''' and continuous infusion of anesthetic agent:
*Place arterial line (Continuous BP monitoring with propofol infusion)
**[[Midazolam]] 0.2 mg/kg IV bolus, then 0.1-2 mg/kg/hr
*Medications (May use propofol as pressure tolerates, otherwise midazolam; Typically start with propofol since may regain neuro exam faster, and add midazolam).  
**[[Propofol]] 2 mg/kg IV bolus, then 2-10 mg/kg/hr (monitor for propofol infusion syndrome)
**IV propofol (causes hypotension)
**[[Pentobarbital]] 5 mg/kg IV bolus, then 1-5 mg/kg/hr
*** 1mg/kg bolus with continued boluses (same dose) every 3-5 minutes until seizures stop (As BP tolerates).  
*Continuous EEG monitoring required
***May place on cIV infusion 1-15 mg/kg/h (Do not exceed >5mg/kg/h in 24 hrs)
*Target: burst-suppression for 24-48 hours
**IV midazolam (less hypotension, longer sedation than propofol)
***0.2mg/kg bolus with repeat boluses  (Same dose) every 5 minutes until seizures stop (max dose 2mg/kg)
***May place on cIV 0.05-2.0 mg/kg/h (up to 200mg/h for 70kg patient).


====> 60 minutes ====
===Special Situations===
*Place in pentobarbital coma
*[[Isoniazid toxicity|INH overdose]]: Pyridoxine (B6) gram-for-gram (empiric 5 g IV if dose unknown)
**5 mg/kg up to 50mg/min. Repeat boluses (same dose) until seizure stop.
*[[Eclampsia]]: Magnesium sulfate 4-6 g IV
**cIV 1mg/kg/h  titrated to suppression on cEEG.
*[[Hyponatremia]]: Hypertonic saline (3%) 100 mL IV bolus


==Disposition==
==Disposition==
*Admit
*ICU admission for all SE patients
 
*Neurology consultation
==External Links==
*Patients with rapidly terminated seizures who return to baseline may be managed on a monitored floor
EM Nerd [http://emnerd.com/adventure-dancing-men/ Adventure of dancing men]


==See Also==
==See Also==
*[[Seizure]]
*[[Seizure]]
*[[First-time seizure]]
*[[Eclampsia]]
*[[Febrile seizure]]
*[[Ethanol withdrawal]]


==References==
==References==
<references/>
<references/>


[[Category:Neuro]]
[[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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