Status Epilepticus

Status Epilepticus (SE)

ILAE Operational Definition (2015)

Status epilepticus is:Generalized tonic-clonic seizure that either lasts >5 minutes or occurs multiple times without regaining normal mental status in between. Or Focal seizure with impaired awareness that lasts >10 minutes.

Two time points are defined:

t1 (Time to Start Treatment)-When seizure is unlikely to stop spontaneously.
t2 (Time of Potential Neuronal Injury)-When permanent neuronal injury may begin.

Type	t1	t2
Generalized convulsive SE	5 min	30 min
Focal impaired-awareness SE	10 min	>60 min
Absence SE	>15 min	Unknown

Table of Contents

Classification

Classification According to Clinical Manifestation

Type	Features
Convulsive Status Epilepticus (CSE)	Most common form; generalized tonic-clonic activity with loss of consciousness; true neurological emergency requiring immediate treatment.
Non-Convulsive Status Epilepticus (NCSE)	Persistent seizure activity without obvious convulsions; presents with confusion, delirium, altered behavior, or coma; diagnosis requires EEG confirmation.

Classification According to EEG and Clinical Features

Type	Examples
Generalized Convulsive SE	Generalized tonic-clonic status epilepticus
Focal Motor SE	Epilepsia partialis continua
Myoclonic SE	Post-anoxic myoclonic status epilepticus
Absence SE	Typical or atypical absence status epilepticus
Focal NCSE	Temporal lobe status epilepticus
Comatose NCSE	Electrographic seizures in comatose ICU patients

Modern Treatment-Based Classification

Type	Definition
Early Status Epilepticus	Seizure duration 0–5 minutes.
Established Status Epilepticus	Seizure duration 5–30 minutes; requires prompt benzodiazepine therapy.
Refractory Status Epilepticus (RSE)	Persistence of seizures despite an adequate dose of a benzodiazepine and one appropriately dosed second-line antiseizure medication.
Super-Refractory Status Epilepticus (SRSE)	Seizures continue for ≥24 hours after initiation of anesthetic therapy or recur during anesthetic withdrawal.

Pathophysiology

Initially:

Excess glutamate excitation
Excess NMDA activation
Increased neuronal firing

With prolonged seizure:

Internalization of GABA receptors
Loss of benzodiazepine responsiveness
Increased excitotoxicity
Neuronal injury

This explains why:

Benzodiazepines become less effective as seizure duration increases.

Etiology

Category	Causes of Status Epilepticus
Acute Cerebrovascular Disease	Ischemic stroke, Intracerebral hemorrhage, Subarachnoid hemorrhage
CNS Infections	Meningitis, Encephalitis, Brain abscess, Neurocysticercosis
Metabolic Disorders	Hypoglycemia, Hyperglycemia, Hyponatremia, Hypernatremia, Hypocalcemia, Hypomagnesemia, Uremia, Hepatic encephalopathy
Antiseizure Medication-Related	Non-compliance, Abrupt withdrawal, Subtherapeutic drug levels
Drug and Toxin-Induced	Tramadol, Bupropion, Theophylline, Isoniazid, Cocaine, Amphetamines, Lithium, Cyclosporine, Tacrolimus
Alcohol-Related	Alcohol withdrawal, Alcohol intoxication
Structural Brain Lesions	Brain tumor, Head trauma, AVM, Post-neurosurgical state
Hypoxic-Ischemic Injury	Cardiac arrest, Severe hypoxemia, Near drowning
Autoimmune Disorders	Anti-NMDA receptor encephalitis, LGI1 encephalitis, CASPR2 encephalitis, GAD antibody-associated encephalitis
Systemic Critical Illness	Sepsis-associated encephalopathy, Multiorgan failure, Severe hypertension/PRES
Pregnancy-Related	Eclampsia, Cerebral venous sinus thrombosis
Genetic/Epileptic Syndromes	Known epilepsy, Developmental epileptic encephalopathies
Degenerative Diseases	Alzheimer’s disease, Cortical degenerative disorders
Idiopathic/Cryptogenic	No identifiable cause despite evaluation
NORSE/FIRES	New-onset refractory status epilepticus, Febrile infection-related epilepsy syndrome
Vitamin deficiency	B1 (thiamine). B6 (pyridoxine). B12.

Causes in ICU

Hypoxia
Hypercapnia
Sepsis-associated encephalopathy
Electrolyte abnormalities
Drug toxicity
Stroke
CNS infection
Medications that lower seizure threshold:

Clinical Features

Phase / Type	Clinical Features
Tonic Phase	Generalized stiffening, Jaw clenching
Clonic Phase	Rhythmic jerking movements
Post-Ictal State	Confusion, Agitation, Coma
Subtle Status Epilepticus	Coma, Eyelid twitching, Nystagmus, Facial twitching; convulsions may disappear despite ongoing EEG seizure activity (common ICU trap)

Complications

System	Complications
Neurological	Neuronal death, Cognitive dysfunction, Epilepsy, Cerebral edema
Cardiovascular	Arrhythmias, Myocardial ischemia, Shock
Respiratory	Aspiration, Hypoxemia, Pulmonary edema
Metabolic	Lactic acidosis, Hyperkalemia, Rhabdomyolysis, AKI

Emergency Evaluation

Immediate Bedside

Within minutes.

ABCDE

Airway
Breathing
Circulation
Disability
Exposure

Fingerstick Glucose

Mandatory.Treat immediately if low.

Initial Investigations

Test	Purpose
CBC	Infection
Electrolytes	Na, Ca, Mg,Phos.
ABG	Acidosis
LFT	Hepatic cause
RFT	Uremia
Toxicology	Drug overdose
Pregnancy test	Women
CK	Rhabdomyolysis
Lactate	Severity
Coagulation studies	INR, PTT
Ammonia level
Creatinine kinase	rhabdomyolysis
Antiseizure medication levels	Valproic acid, phenobarbital, and phenytoin
Urinalysis

Neuroimaging

CT Brain is generally indicated.
CT venogram if concern for cerebral venous thrombosis
Indications to additionally get a CT angiogram include:

New focal neurological deficit.
Persistent coma.
Another reason to suspect an ischemic stroke.
Unable to obtain an MRI

When CT Brain Should Be Performed Urgently

Indication	Reason
First episode of status epilepticus	Rule out structural lesion
New focal neurological deficit	Stroke, hemorrhage, mass lesion
Head trauma	Intracranial bleeding
Persistent altered consciousness	Structural pathology, cerebral edema
Suspected stroke	Ischemic or hemorrhagic stroke
Immunocompromised patient	CNS infection, abscess
Known malignancy	Brain metastasis
Anticoagulation use	Intracranial bleed

When CT May Not Be Immediately Necessary

Situation	Comments
Known epilepsy with typical breakthrough seizure and clear trigger (e.g., medication non-compliance)	Imaging may not be urgently required if patient returns to baseline
Established epilepsy with recurrent identical seizures and no new neurological findings	Imaging can be deferred
Clear metabolic cause (e.g., severe hypoglycemia, profound hyponatremia) with complete recovery	Imaging may not be immediately needed

MRI Brain

More sensitive.

Detects:

Encephalitis
Autoimmune disease
Tumor
Temporal lobe pathology

EEG

Gold standard.

Indications:

Persistent altered sensorium
Suspected NCSE
Refractory SE
ICU coma

Continuous EEG is preferred.

Lumbar puncture

The primary indication is typically the exclusion of meningitis or encephalitis(if any signs or symptom present).Consider obtaining an autoimmune encephalitis panel and oligoclonal bands.Note that prolonged status epilepticus itself can cause elevation of protein and total cell count (but not above ~80-100/mm3).

Management

Step 1: Stabilization

Airway

Intubation if:

GCS ≤8
Ongoing seizures
Aspiration risk
Need for anesthetics

Oxygen

100% oxygen.

IV Access

Two large-bore lines.

Glucose

Thiamine 100 mg IV Then Dextrose 25 g
If active thiamine deficiency: 500 mg IV q8hr.
To prevent the development of thiamine deficiency: 100 mg IV daily.

Pyridoxine

180-600 mg daily (PO or IV).

Pharmacologic Treatment

First-Line Therapy (0–10 Minutes)-Benzodiazepines

Drug	Dose	Key Points
Lorazepam (Preferred)	0.1 mg/kg IV (maximum 4 mg per dose)	First-line drug for status epilepticus; may repeat once after 5–10 minutes if seizures persist.
Diazepam	0.15–0.2 mg/kg IV (maximum 10 mg per dose)	(may repeat once q5-10 minutes),Rapid onset but shorter duration due to redistribution; often followed by a longer-acting antiseizure medication.
Midazolam	IM: 10 mg (adults >40 kg) ,5 mg (13–40 kg) IV: 0.2 mg/kg Intranasal/Buccal: 0.2 mg/kg	Preferred when IV access is unavailable

These doses will not cause respiratory Depression.adequate doses of benzodiazepines may reduce the need for intubation.
Even if the benzodiazepine breaks the seizure, you still need to give the patient a maintenance antiseizure medication.
ketamine(100 mg) is useful as a 2nd-line treatment for seizure control in non-intubated patients.

Second-Line Therapy (10–30 Minutes)-Choose ONE.

Drug	Dose	Important Points
Levetiracetam(first line)	L.D 60 mg/kg IV (maximum 4.5 g)-Usually infused over 10–15 min. Maintenance—1.5gm-4.5gm/day divided q6hr-q12h	Minimal drug interactions No absolute contraindications. Renal dose adjustment Needed S/E-Mood disturbance, agitation, psychosis
Valproate	Loading dose-40 mg/kg IV(Max dose-Usually 3 g over 5–15 min). Maintenance-15-60 mg/kg divided in TDS or QID	Contraindication—severe liver disease, pregnancy,hyperammonemia,Thrombocytopeni Avoid combining valproic acid with fosphenytoin, carbapenems, lamotrigine, or topiramate.
Fosphenytoin	Loading Dose—20 mg PE/kg IV(maximum 1500 mg PE),rate of 150 PE/min Maintenance Dose-1.66-2.33 PE/kg IV q8hr (e.g., ~100 mg IV q8hr.	Contraindications-Pregnancy,Hepatic dysfunction:Relative contraindication;Renal dysfunction is a relative contraindication,Hypotension,Bradycardia,Cardiac conduction abnormalities,Toxicological seizures (e.g., seizures due to cocaine, local anesthetics, lindane, or theophylline),Absence or myoclonic seizures may be exacerbated by phenytoin.
Phenytoin	20 mg/kg IV (infusion rate ≤50 mg/min,≤25 mg/min in elderly/cardiac disease) Max dose-Usually 2 g	Requires ECG and blood pressure monitoring; risks include hypotension, arrhythmias, and extravasation injury.
Phenobarbital	Loading-15–20 mg/kg IV(100 mg/min),can repeat,Max cumulative dose dose-30 mg/kg Maintenance—2-3 mg/kg/day divided q12hr.	Contraindications-Pregnancy,Advanced Cirrhosis,Acute intermittent porphyria,Patient on sedatives. S/E—Respiratory suppression,Hypotension Renal failure and/or hepatic failure: Follow phenobarbital levels and re-dose accordingly.
Lacosamide(second line)	Loading dose —400 mg IV over 5 min(8 mg/kg, max 600 mg). If the seizure continues, an additional 5 mg/kg (max 250 mg) or 200 mg over 5 minutes may be given. Maintenance-200 mg IV B.D or TDS.	Contraindications-Clinical sick sinus syndrome without a pacemaker,2nd-degree heart block,Marked 1st-degree heart block,Severe hepatic dysfunction (Child-Pugh class C). If GFR<30 ml/min, reduce dosage by 25%.

Selecting an antiseizure medication in status epilepticus

If the patient is adherent to chronic antiseizure therapy: Consider an IV loading dose of a different appropriate antiseizure medication, taking into account the chronic drug, seizure type, comorbidities and contraindications. For example, IV lacosamide may be considered in a patient already receiving levetiracetam.
If non-adherence or inadequate drug exposure is suspected: Reloading the patient’s usual antiseizure medication may be appropriate if it is suitable for acute loading. Consider drug levels when available and clinically useful. Use particular caution with phenobarbital because accumulation can cause prolonged sedation and respiratory depression.
When the choice is uncertain: IV levetiracetam is often a practical option because of its favorable interaction profile and generally limited cardiovascular effects. However, it is not universally the best drug, and dosing should account for renal function and clinical context.

Evidence (ESETT Trial)

The landmark ESETT trial showed:Levetiracetam,Fosphenytoin,Valproate

have similar efficacy (~45–50%).Therefore current guidelines allow any of these as second-line therapy.

Refractory Status Epilepticus

Failure of:Benzodiazepine PLUS One second-line agent
Intubate and initiate continuous EEG.neurologist consult
A common ICU mistake is to assume that if the motor activity stops after paralysis, the seizure has stopped. Neuromuscular blockers do not treat seizures. They only abolish the motor manifestations while electrographic seizure activity may continue unabated.
Following intubation, rocuronium may be reversed with sugammadex to allow for neurological examination.
Each time seizures recur, you should add or dose-escalate the maintenance antiseizure medication regimen.

Continuous Anesthetic Infusions

Anesthetic Agent	Dose	Important Points
Midazolam	Loading: 0.2 mg/kg IV Infusion: 0.05–2 mg/kg/hr	Tachyphylaxis present Not Preferred as not able to rapidly awaken and wean patients off ventilation.
Propofol(first line)	Loading:2 mg/kg IV(up to 200 mg)May repeat q3-5 minutes if hemodynamically tolerated, to a total dose of 10 mg/kg. Infusion: 20–200 µg/kg/min	Rapid onset and rapid offset; monitor for Propofol Infusion Syndrome (PRIS). If abruptly stopped, patients may have a rebound seizure.
Ketamine(second line)	Loading: 1–2mg/kg IV,every 5 minutes, up to a total cumulative dose of 5 mg/kg Infusion: 1–7.5 mg/kg/hr	Increasingly favored; NMDA receptor antagonist, causes less hypotension. Useful in super-refractory status epilepticus.
Pentobarbital Coma	Loading: 5–15 mg/kg IV at 50 mg/min. (followed by continuous infusion 0.5–5 mg/kg/hr)	Last-line agent for super-refractory status epilepticus. Major complications include profound hypotension, immunosuppression, and ileus. Continuous EEG monitoring is necessary
Thiopentone	Thiopentone Loading 2–5 mg/kg,Infusion 1–5 mg/kg/hr

EEG Targets During Anesthetic Therapy

Common targets:

Seizure suppression
Burst suppression
Complete EEG suppression

No clear superiority of one strategy.

Maintenance Antiseizure Therapy

Even while on anesthetic infusions, multiple antiseizure drugs are continued.

Common combinations:

Levetiracetam + Valproate
Levetiracetam + Lacosamide
Levetiracetam + Fosphenytoin
Triple therapy in difficult cases

How Long Should EEG Suppression Be Maintained?

Most guidelines recommend:24 Hours of No electrographic seizures before attempting weaning.Longer (48 hours) if SRSE.The optimal rate of weaning from anesthetic infusions is unknown but don’t stop infusion abruptly taper off over 6-12 hours.

What If Seizures Recur During Weaning?

This is very common.Patient now effectively has:Super-Refractory Status Epilepticus
Increase anesthetic back to effective dose.

Super-Refractory Status Epilepticus

Refractory to two antiseizure medications and anesthetic therapy for >24 hours or when seizures reemerge during an attempted anesthetic wean.Prolonged super-refractory status epilepticus (PSRSE): Super-refractory status epilepticus that lasts for >7 days, including ongoing need for anesthetics.

Additional Therapies

Ketogenic Diet-4:1 fat-to-carbohydrate/protein ratio

Particularly useful in:

NORSE
FIRES

Immunotherapy

If autoimmune encephalitis suspected.

Methylprednisolone-1 g/day × 3–5 days
IVIG-0.4 g/kg/day × 5 days
Plasma Exchange-5–7 exchanges

Useful in antibody-mediated disease.

Biologic Therapy

Selected cases:

Rituximab
Cyclophosphamide
Tocilizumab
Anakinra

Neuromodulation

Vagus Nerve Stimulation (VNS)

May help persistent SRSE.

Usually considered:After medical failure

Deep Brain Stimulation

Rare rescue therapy.

Electroconvulsive Therapy (ECT)

Occasionally effective.

Used only in extreme SRSE.

Surgical Therapy

Consider when focal epileptogenic lesion identified.

Options:

Focal resection
Lobectomy
Hemispherectomy (rare)

Particularly useful:

Tumors
Cortical dysplasia
Focal encephalitis

NORSE(New-Onset Refractory Status Epilepticus)

Definition:Refractory SE(i.e., refractory to two medications such as benzodiazepine plus levetiracetam). occurring in a person without previous epilepsy and without obvious acute cause.
causes of NORSE
Non-paraneoplastic autoimmune (e.g., anti-NMDA encephalitis).
Paraneoplastic.
Infectious.

management

Early empiric therapy may be considered.
High-dose methylprednisolone (1 gram/day over 3-5 days).
Either plasma exchange (5-7 exchanges) or IVIG (0.4 g/kg/day for five days).

FIRES(Febrile Infection-Related Epilepsy Syndrome)

A subtype of NORSE.

Typically:

Previously healthy
Viral-like illness
Explosive refractory seizures

High mortality.

Psychogenic nonepileptic seizures (PNES) — “Pseudoseizures”

Preferred term: Psychogenic nonepileptic seizures (PNES), also called functional seizures. The term pseudoseizures is discouraged because it can imply that the events are fabricated.

PNES are episodes that resemble epileptic seizures but occur without the abnormal cortical electrical activity characteristic of an epileptic seizure. They are classified as functional neurological disorder and are not necessarily intentional or under the patient’s conscious control.

1. PNES vs epileptic seizures

Feature	PNES	Epileptic seizure
Onset	May be gradual	Often abrupt
Movements	Variable, asynchronous, waxing and waning,Irregular eye movements	Often stereotyped and rhythmic
Eyes	Often closed, with resistance to opening	Often open during bilateral tonic-clonic seizures
Responsiveness/Consiousness	May fluctuate during the event,preservation of consciousness	Usually impaired in bilateral tonic-clonic seizures
Duration	Often prolonged or fluctuating	Typically more stereotyped; prolonged seizures can occur
Postictal state	Recovery may be rapid or variable	Confusion and sleepiness may occur
Lateral tongue bite	Less typical	More supportive, especially with other features
EEG during event	No epileptic ictal correlate on interpretable video-EEG	Ictal epileptiform activity may be present

Important: No single clinical feature reliably distinguishes PNES from epilepsy. Epilepsy and PNES can coexist, and some epileptic seizures may lack a clear scalp EEG correlate.

2. How to confirm the diagnosis

Gold standard: Video-EEG recording of a typical event, showing compatible clinical features without an epileptic ictal EEG correlate.
A normal routine interictal EEG does not exclude epilepsy and does not establish PNES.
Serum prolactin and lactate may provide supportive information in selected circumstances but cannot reliably confirm or exclude PNES.

3. Why PNES matters in status epilepticus

Suspected PNES can be mistaken for refractory status epilepticus, resulting in repeated benzodiazepines, antiseizure drug loading, intubation and ICU admission.

If a patient has prolonged seizure-like movements but is physiologically stable and the clinical pattern suggests PNES:

Assess airway, breathing, circulation, glucose and potential injuries.
Observe the event carefully and obtain a witness or smartphone video when feasible.
Seek urgent neurological assessment and EEG when the diagnosis remains uncertain.
Avoid escalating antiseizure medications or inducing anaesthesia solely because movements persist when PNES is strongly suspected and the patient is stable.

Safety rule: If true convulsive status epilepticus remains plausible, treat it promptly. Do not delay treatment for EEG, and do not assume that a patient with previously diagnosed PNES cannot also develop epileptic seizures.

4. Treatment

Explain the diagnosis clearly and respectfully; the episodes are real and not necessarily intentional.
Arrange neurological follow-up and psychological or psychiatric assessment as appropriate.
Psychological interventions, including cognitive behavioural approaches, may help reduce seizure frequency and improve quality of life.
Antiseizure medications do not treat PNES itself and should be discontinued only when epilepsy or another indication has been appropriately excluded and the prescribing clinician supervises the change.