# Status Epilepticus: Emergency Management

## Introduction

Status epilepticus (SE) is a neurologic emergency defined as continuous seizure activity lasting 5 minutes or longer, or two or more seizures without return to baseline between episodes. Convulsive SE carries a mortality rate of 10-30% and the risk of permanent neurologic injury increases with each minute of ongoing seizure activity. A structured, time-based protocol with immediate benzodiazepine administration is critical to improving outcomes.

## Definitions and Classification

- **Convulsive status epilepticus (CSE)**: continuous generalized tonic-clonic seizure activity >= 5 minutes
- **Non-convulsive status epilepticus (NCSE)**: electrographic seizure activity without prominent motor manifestations; often presents as altered mental status, confusion, or subtle eye movements
- **Refractory SE (RSE)**: seizures persisting despite adequate first-line (benzodiazepine) and second-line antiseizure medication
- **Super-refractory SE (SRSE)**: seizures continuing >= 24 hours after initiation of anesthetic agents, or recurring upon anesthetic withdrawal
- **Established SE**: seizures lasting >= 30 minutes without treatment; associated with excitotoxic neuronal injury, receptor trafficking (GABA receptor internalization, NMDA receptor externalization), and progressive pharmacoresistance

## Etiology

### Common Causes in Adults

- **Antiseizure medication (ASM) non-adherence or withdrawal**: most common cause in known epilepsy patients
- **Acute structural lesion**: stroke, hemorrhage, traumatic brain injury, brain tumor
- **CNS infection**: meningitis, encephalitis (HSV), brain abscess
- **Metabolic derangements**: hypoglycemia, hyponatremia, hypocalcemia, uremia, hepatic encephalopathy
- **Toxic exposures**: alcohol withdrawal, benzodiazepine withdrawal, drug overdose (sympathomimetics, isoniazid)
- **Autoimmune encephalitis**: anti-NMDA receptor encephalitis, LGI1 antibody encephalitis
- **Anoxic brain injury**: post-cardiac arrest

![Etiologic categories of status epilepticus](images/se-etiology.png)

## Time-Based Treatment Protocol

### Phase 1: Stabilization (0-5 Minutes)

- **ABCs**: secure airway, suction secretions, position in lateral decubitus, supplemental oxygen
- **IV access**: obtain two large-bore IVs
- **Fingerstick glucose**: administer **dextrose 50% (25-50 mL IV)** if hypoglycemic
- **Thiamine 100 mg IV** before or with dextrose (if alcoholism or malnutrition suspected)
- **Labs**: BMP, CBC, calcium, magnesium, ASM levels, toxicology screen, ABG
- **Do NOT**: place objects in the mouth, restrain the patient forcefully

### Phase 2: First-Line Therapy -- Benzodiazepines (5-20 Minutes)

| Agent | Route | Dose | Notes |
|-------|-------|------|-------|
| Lorazepam | IV | 0.1 mg/kg (max 4 mg), repeat x1 in 5 min | Preferred IV agent |
| Midazolam | IM | 10 mg (>40 kg) | Preferred if no IV access (RAMPART) |
| Diazepam | IV | 0.15 mg/kg (max 10 mg) | If lorazepam unavailable |
| Midazolam | Intranasal | 5 mg per nostril | Alternative non-IV route |
| Diazepam | Rectal | 0.2 mg/kg | Alternative non-IV route |

- **IV lorazepam**: 0.1 mg/kg (max 4 mg), repeat once in 5 minutes if seizures continue
- **IM midazolam**: 10 mg IM (> 40 kg) if no IV access; **RAMPART trial** demonstrated IM midazolam non-inferior to IV lorazepam with faster time-to-treatment in the prehospital setting
- **IV diazepam**: 0.15 mg/kg (max 10 mg) if lorazepam unavailable
- **Rectal diazepam** or **intranasal midazolam**: alternatives when IV/IM access is not available
- Benzodiazepines terminate seizures in approximately 65% of cases when given promptly

### Phase 3: Second-Line Therapy -- Urgent Control (20-40 Minutes)

If seizures persist after adequate benzodiazepine doses:

| Agent | Dose | Infusion Rate | Avoid If |
|-------|------|---------------|----------|
| Levetiracetam | 60 mg/kg (max 4500 mg) | Over 10 min | Few contraindications |
| Fosphenytoin | 20 mg PE/kg | 150 mg PE/min | Cardiac conduction disease, bradycardia |
| Valproate | 40 mg/kg (max 3000 mg) | Over 10 min | Pregnancy, hepatic failure, mitochondrial disease |

- **IV levetiracetam**: 60 mg/kg (max 4500 mg) infused over 10 minutes; fewest drug interactions, no hemodynamic effects
- **IV fosphenytoin**: 20 mg PE/kg at 150 mg PE/min; monitor for hypotension and arrhythmia; avoid in known cardiac conduction disease
- **IV valproate**: 40 mg/kg (max 3000 mg) infused over 10 minutes; avoid in pregnancy, hepatic failure, mitochondrial disease, pancreatitis
- **ESETT trial**: levetiracetam, fosphenytoin, and valproate are equally effective as second-line agents (seizure cessation in approximately 45% each); choice should be based on patient-specific factors

### Phase 4: Refractory SE -- Third-Line Therapy (> 40 Minutes)

- **Intubation and continuous IV anesthetic infusion**:
  - **Midazolam**: 0.2 mg/kg bolus, then 0.1-2 mg/kg/hour infusion
  - **Propofol**: 2 mg/kg bolus, then 30-200 mcg/kg/min; monitor for propofol infusion syndrome (metabolic acidosis, rhabdomyolysis, cardiac failure) if > 48 hours or > 5 mg/kg/hour
  - **Pentobarbital**: 5 mg/kg bolus, then 1-5 mg/kg/hour; most potent but greatest hemodynamic compromise
- **Continuous EEG (cEEG) monitoring**: mandatory to guide anesthetic titration; target **burst suppression** or **seizure suppression**
- Maintain anesthetic infusion for **24-48 hours**, then slowly wean while monitoring for seizure recurrence

![Time-based status epilepticus treatment algorithm](images/se-treatment-algorithm.png)

## Non-Convulsive Status Epilepticus

- Suspect in any patient with **unexplained altered mental status**, particularly after convulsive seizures
- Diagnosis requires **continuous EEG monitoring**
- Common in the ICU: up to 20% of comatose ICU patients have NCSE
- Treat with the same stepwise protocol, though urgency may be slightly less than in convulsive SE
- Post-cardiac arrest: electrographic seizures common but treatment decisions are complex; avoid aggressive anesthetic therapy if prognosis is poor

## Special Considerations

- **Isoniazid toxicity**: treat with **pyridoxine (vitamin B6)** gram-for-gram replacement (5 g IV if dose unknown)
- **Eclampsia**: **magnesium sulfate** is the agent of choice (not benzodiazepines)
- **Alcohol withdrawal seizures**: typically self-limited; benzodiazepines are first-line; phenobarbital is an effective alternative
- **Anti-NMDA receptor encephalitis**: immunotherapy (steroids, IVIG, plasmapheresis) alongside ASMs

## Key Clinical Pearls

- Give benzodiazepines IMMEDIATELY; every minute of delay reduces the probability of seizure termination
- IM midazolam is as effective as IV lorazepam and can be administered faster when IV access is not established (RAMPART trial)
- Levetiracetam, fosphenytoin, and valproate are equally effective second-line agents (ESETT trial); choose based on comorbidities and drug interactions
- Always obtain continuous EEG monitoring in refractory SE and in any patient who does not return to baseline mental status after seizure cessation

## References

1. Glauser T, Shinnar S, Gloss D, et al. Evidence-Based Guideline: Treatment of Convulsive Status Epilepticus in Children and Adults (AAN/AES). *Epilepsy Curr*. 2016;16(1):48-61.
2. Kapur J, Elm J, Chamberlain JM, et al. Randomized Trial of Three Anticonvulsant Medications for Status Epilepticus (ESETT). *N Engl J Med*. 2019;381(22):2103-2113.
3. Silbergleit R, Durkalski V, Lowenstein D, et al. Intramuscular versus Intravenous Therapy for Prehospital Status Epilepticus (RAMPART). *N Engl J Med*. 2012;366(7):591-600.
4. Brophy GM, Bell R, Claassen J, et al. Guidelines for the Evaluation and Management of Status Epilepticus. *Neurocrit Care*. 2012;17(1):3-23.