← EMA Topics
EMA Topics · Neurology · Resuscitation

Status epilepticus

Updated Oct 17, 2026Adults · ED management23 sources · 18 checked in PubMed1 figureACEP 2024 · AES 2016

Bottom line

  • Five minutes is the trigger. Treat a convulsion lasting 5 minutes or more, or repeated seizures without a return to baseline, as status epilepticus.1,2
  • One full benzodiazepine dose, by the fastest route. Without an IV, IM midazolam 10 mg (over 40 kg) is the choice. It stopped more prehospital seizures than IV lorazepam (73.4% vs 63.4%).2,3
  • Underdosing is the usual error. In ESETT, the first dose was below the guideline dose in 76% of midazolam and 81% of lorazepam doses.4 Withholding benzodiazepines is not safer: in a paramedic trial, respiratory or circulatory complications occurred in 22.5% with placebo vs about 10% with a benzodiazepine (P = 0.08).5
  • Second line: levetiracetam, fosphenytoin or valproate, as one full load. Each stopped seizures in about half of patients (47%, 45%, 46%). ACEP calls them similar (Level A).6,1
  • Still seizing at 40 minutes? Start an anesthetic infusion with continuous EEG. After convulsions stop, a patient who stays unresponsive may still be seizing: 48% had ongoing electrographic seizures in one cohort.2,7,8

First 5 minutes

  1. Note the time the seizure started. Treatment steps follow the clock.2
  2. Airway, breathing, circulation, neuro exam. Give oxygen by nasal cannula or mask. Consider intubation if breathing needs support.2
  3. Monitor: vital signs and ECG.2
  4. Check a fingerstick glucose. If it is under 60 mg/dL, give thiamine 100 mg IV, then 50 mL of D50 IV.2
  5. Try for IV access. Send electrolytes, blood counts, a toxicology screen and, when relevant, antiseizure drug levels.2
  6. Still seizing at 5 minutes: give a benzodiazepine now. Don't wait for the IV. Use IM midazolam if there is no line.2,3

Definitions and timing

  • Status epilepticus: a seizure lasting more than 5 minutes, or several seizures without a return to neurologic baseline between them.1
  • Two time points. For convulsive seizures, after 5 minutes (t1) a seizure is unlikely to stop on its own. After 30 minutes (t2), the risk of long-term harm, such as neuronal injury, begins. Both are best estimates.9
  • Established status: still seizing after an adequate benzodiazepine dose. ESETT enrolled patients still convulsing 5 to 30 minutes after the last dose.10
  • Refractory status: seizures continue despite at least two antiseizure drugs, usually including a benzodiazepine. Super-refractory: seizures continue despite at least one course of anesthetic.7
FIG 1The status epilepticus clock. Drawn for this page from the phases in the American Epilepsy Society algorithm. Move faster, or skip the second phase, when the patient is very sick.2 The times are targets, not waiting periods.

Treatment

DrugAdult doseNotes
Initial therapy (from 5 min): choose one benzodiazepine
Midazolam IM10 mg once (over 40 kg)Best choice without an IV. Single dose.2,3
Lorazepam IV0.1 mg/kg, max 4 mg; may repeat onceLabel: 4 mg given at 2 mg/min; another 4 mg if seizures persist after 10–15 min.2,11
Diazepam IV0.15–0.2 mg/kg, max 10 mg; may repeat onceEquivalent first-line option.2
If none of these is available
Phenobarbital IV15 mg/kg onceEffective, but slower to give.2
Diazepam rectal0.2–0.5 mg/kg, max 20 mg, oncePrehospital or no other option.2
Midazolam intranasal or buccalDose per institutional protocol and labelPrehospital or no other option.2
Second therapy (from 20 min): choose one, give as one load
Levetiracetam IV60 mg/kg, max 4,500 mgACEP lists only hypersensitivity as a contraindication.1,2
Fosphenytoin IV20 mg PE/kg, max 1,500 mg PENo faster than 150 mg PE/min, with cardiac monitoring. Avoid in AV block or sinus bradycardia.1,2,12
Valproate IV40 mg/kg, max 3,000 mgAvoid in liver disease. Contraindicated in POLG mitochondrial disease and urea cycle disorders. Fetal risk.1,2,13
Phenobarbital IV15 mg/kg onceOnly if none of the three above is available.2
Third therapy (from 40 min)
Repeat second line, or anesthetic infusion (midazolam, propofol, pentobarbital, thiopental)Dose per institutional protocol and labelUse continuous EEG.2 Midazolam or propofol are preferred.7

Unreviewed doses. Verify against the current label and your institution's protocol before giving anything.

Doses from the American Epilepsy Society algorithm.2 The second-line doses and maximums match ACEP's table, and ESETT gave each over 10 minutes.1 PE means phenytoin sodium equivalents. The fosphenytoin label allows 15–20 mg PE/kg at 100–150 mg PE/min for status epilepticus.12

Benzodiazepines

  • They are the first-line drugs (Level A). Give one full dose, not several small ones. Only IV lorazepam or IV diazepam may be repeated, and only once.2
  • IM midazolam vs IV lorazepam (RAMPART, n = 893 adults and children): seizures had stopped by ED arrival in 73.4% vs 63.4%. The IM drug went in faster (median 1.2 vs 4.8 minutes), though IV lorazepam worked faster once given (3.3 vs 1.6 minutes). Intubation rates were the same (14.1% vs 14.4%).3
  • Benzodiazepines vs placebo by paramedics (n = 205 adults): status had stopped by ED arrival in 59.1% with lorazepam, 42.6% with diazepam and 21.1% with placebo. Respiratory or circulatory complications were 10.6%, 10.3% and 22.5% (P = 0.08).5
  • Lorazepam vs phenytoin first (VA trial, overt status): lorazepam worked in 64.9%, phenobarbital in 58.2%, diazepam plus phenytoin in 55.8% and phenytoin alone in 43.6%.14
  • Underdosing is widespread. In 2,494 prehospital patients, none got midazolam at a guideline dose and route. Higher doses meant less rescue dosing (OR 0.8) and no more respiratory support.15

Second-line drugs

  • ESETT (n = 384): seizures stopped with better alertness at 60 minutes in 47% with levetiracetam, 45% with fosphenytoin and 46% with valproate. Safety did not differ significantly.6
  • By age (n = 462): in adults 18–65, success was 44%, 46% and 46%. In adults over 65, it was 37%, 35% and 47%. No drug differed within any age group.10
  • Harms in ESETT: life-threatening hypotension in 0.7% (levetiracetam), 3.2% (fosphenytoin) and 1.6% (valproate). Intubation in 20%, 26.4% and 16.8%. None of these differences was significant.1
  • ACEP 2024 (Level A): treat seizures that persist after appropriately dosed benzodiazepines with a second-line drug. Fosphenytoin, levetiracetam or valproate may be used with similar efficacy.1
  • Prehospital levetiracetam added nothing. Adding 2.5 g of levetiracetam to clonazepam stopped convulsions in 74% vs 84% with clonazepam alone, a nonsignificant difference.16
Sources disagree

Before ESETT, the American Epilepsy Society found no preferred second drug. It rated valproate Level B and fosphenytoin and levetiracetam Level U (insufficient data).2 After ESETT, ACEP rates all three as similar at Level A.1 The AES also uses phenobarbital 15 mg/kg, while noting that other consensus guidelines often use 20 mg/kg.2

Refractory status epilepticus

  • How common: in about one third of patients, seizures do not stop after a benzodiazepine and a second drug.17 Super-refractory status is about one in twenty episodes.7
  • Why it matters: short-term mortality is about 10% when status responds, about 25% when it is refractory, and nearly 40% when it is super-refractory.7
  • Options from 40 minutes: repeat a second-line drug, or give anesthetic doses of midazolam, propofol, pentobarbital or thiopental, all with continuous EEG. No clear evidence guides this step (Level U).2
  • Midazolam or propofol first. Neither has shown clear superiority. Concern about propofol infusion syndrome favors midazolam, or lower-dose propofol combined with midazolam.7
  • EEG target: stop the seizures. Burst suppression is not routinely required, and deeper sedation has not improved seizure control. Guidelines suggest 24–48 hours of sedation after control, then a taper with EEG.7
  • Other drugs: lacosamide is possibly effective (Level C). Evidence for ketamine is insufficient (Level U).17
  • Intubation: avoid neuromuscular blockers where possible. If one is needed, LITFL suggests short-acting succinylcholine. Use EEG for patients who do not wake.18

Workup and causes

  • Bedside: glucose and a blood gas. Labs: electrolytes including sodium and calcium, renal function, blood counts, toxicology and antiseizure drug levels.2,18
  • Imaging: get brain imaging, along with a broad lab workup, quickly to find the cause.7
  • Lumbar puncture: prolonged seizures alone can raise the CSF white count above 100 without infection.18
  • Common causes: stroke, tumor, trauma, toxic-metabolic problems and anoxic injury.7 Missed antiseizure doses are a frequent trigger, and drugs such as tramadol and cocaine lower the seizure threshold.1
  • Toxins: in ESETT, 11.6% of adults had toxin-related seizures, most often alcohol withdrawal or cocaine.19 ACEP finds too little data to guide drug choice here and notes fosphenytoin may not work.1
  • Special causes: eclampsia needs magnesium, blood pressure control and delivery. Isoniazid overdose needs pyridoxine.18 Magnesium has only case reports in other refractory status.17
  • Psychogenic nonepileptic seizures: 10% of ESETT patients had them.6 Clues include eyes held shut, asymmetric movements and pelvic thrusting.18
Not waking up is not always postictal

With EEG for at least 24 hours after convulsive status was controlled, 48% of 164 patients had persistent electrographic seizures, and more than 14% were in nonconvulsive status. The patients in nonconvulsive status were comatose with no visible convulsions.8 Up to 48 hours of EEG detects 95% of ICU seizures.7 Telling postictal patients from nonconvulsive status is hard in the ED without EEG.1

Disposition

  • Most patients need a high-dependency or ICU bed and a neurology consult.18
  • Not back to baseline after convulsions stop: arrange continuous EEG.18,8
  • Refractory status on an anesthetic infusion: ICU, with EEG monitoring for at least 24 hours after the taper.7
  • Back to baseline: the AES algorithm moves to symptomatic medical care.2 Seizures recurred in about 11% of RAMPART patients, so keep watching.3

Pitfalls

  • Giving lorazepam 1–2 mg at a time. Most patients in ESETT were underdosed.4
  • Waiting for IV access instead of giving IM midazolam.2,3
  • Holding benzodiazepines for fear of respiratory depression. Untreated seizures caused more complications than benzodiazepines.5,15
  • Pushing fosphenytoin faster than 150 mg PE/min. It risks severe hypotension and arrhythmias.12
  • Giving valproate in liver disease or pregnancy without weighing the risks.1,13
  • Calling persistent coma "postictal" without EEG.8,1
  • Forgetting the fingerstick glucose.2

How strong is the evidence?

  • First line is strong. Benzodiazepines rest on several class I randomized trials (Level A).2
  • Second line rests on one trial. ACEP's review found 1,176 articles, but only 3 papers met its criteria, all from ESETT.1 ESETT judged success clinically, not by EEG.1 Reviewers also flagged frequent eligibility deviations and unblinding in 200 of 400 enrollments.20
  • Refractory status rests mostly on case series (class IV studies) for every anesthetic.17
  • Guidelines agree on early and refractory treatment. A review of 15 adult guidelines found less agreement on established and super-refractory status.21
  • Children: in two pediatric trials, levetiracetam was not superior to phenytoin (ConSEPT 50% vs 60%; EcLiPSE 70% vs 64%).22,23

On-shift teaching

Questions to ask a learner at the bedside. Tap a question to see the answer. Every answer uses facts cited above.

Q1A 70 kg man is still convulsing at 5 minutes and has no IV. What do you give?
IM midazolam 10 mg, once.2 In RAMPART it stopped more seizures by ED arrival than IV lorazepam (73.4% vs 63.4%). It went in faster (median 1.2 vs 4.8 minutes), though lorazepam worked faster once given.3
Q2Why not give lorazepam 1 mg at a time and see?
The AES advises one full dose, not small divided ones.2 Underdosing is common: the first dose was low in 81% of lorazepam doses in ESETT.4 Higher midazolam doses meant less rescue dosing and no more respiratory support.15
Q3Which second-line drug works best?
None clearly. In ESETT, levetiracetam, fosphenytoin and valproate each worked in about half of patients (47%, 45%, 46%).6 ACEP rates them as similar (Level A).1
Q4How fast can you give fosphenytoin, and why does it matter?
No faster than 150 mg PE/min in adults. Faster rates risk severe hypotension and arrhythmias, so monitor the heart during and after.12
Q5The convulsions stopped 30 minutes ago, but she still doesn't respond. What are you worried about?
Nonconvulsive status. After convulsive status was controlled, 48% of patients had ongoing electrographic seizures and more than 14% were in nonconvulsive status.8 Get continuous EEG.18
Q6Define refractory and super-refractory status epilepticus.
Refractory: seizures continue despite at least two antiseizure drugs, usually including a benzodiazepine. Super-refractory: seizures continue despite at least one course of anesthetic. Short-term mortality is about 25% and nearly 40%.7

References

  1. 1
    American College of Emergency Physicians Clinical Policies Subcommittee on Seizures; Smith MD, Sampson CS, Wall SP, Diercks DB. Clinical Policy: Critical issues in the management of adult patients presenting to the emergency department with seizures. Ann Emerg Med. 2024;84(1):e1–e12.GuidelinePMID 38906639acep.org (PDF)Full text read
  2. 2
    Glauser T, Shinnar S, Gloss D, et al. Evidence-based guideline: treatment of convulsive status epilepticus in children and adults. Report of the Guideline Committee of the American Epilepsy Society. Epilepsy Curr. 2016;16(1):48–61. Treatment algorithm on aesnet.org.GuidelinePMID 26900382PMCaesnet.orgFull text read
  3. 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.RCTPMID 22335736PMCPubMed
  4. 4
    Sathe AG, Underwood E, Coles LD, et al. Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial. Epilepsia. 2021;62(3):795–806.CohortPMID 33567109PMCPubMed
  5. 5
    Alldredge BK, Gelb AM, Isaacs SM, et al. A comparison of lorazepam, diazepam, and placebo for the treatment of out-of-hospital status epilepticus. N Engl J Med. 2001;345(9):631–637.RCTPMID 11547716PubMed
  6. 6
    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.RCTPMID 31774955PMCPubMed
  7. 7
    Rossetti AO, Claassen J, Gaspard N. Status epilepticus in the ICU. Intensive Care Med. 2024;50(1):1–16.ReviewPMID 38117319PMCFull text read
  8. 8
    DeLorenzo RJ, Waterhouse EJ, Towne AR, et al. Persistent nonconvulsive status epilepticus after the control of convulsive status epilepticus. Epilepsia. 1998;39(8):833–840.CohortPMID 9701373PubMed
  9. 9
    Trinka E, Cock H, Hesdorffer D, et al. A definition and classification of status epilepticus: report of the ILAE Task Force on Classification of Status Epilepticus. Epilepsia. 2015;56(10):1515–1523.ConsensusPMID 26336950PubMed
  10. 10
    Chamberlain JM, Kapur J, Shinnar S, et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet. 2020;395(10231):1217–1224.RCTPMID 32203691PMCPubMed
  11. 11
    Ativan (lorazepam) injection. US prescribing information. Hikma Pharmaceuticals USA Inc. DailyMed.Drug labeldailymed.nlm.nih.govLabel text read
  12. 12
    Fosphenytoin sodium injection. US prescribing information. Glenmark Pharmaceuticals Inc., USA. DailyMed.Drug labeldailymed.nlm.nih.govLabel text read
  13. 13
    Valproate sodium injection. US prescribing information. Sagent Pharmaceuticals. DailyMed.Drug labeldailymed.nlm.nih.govLabel text read
  14. 14
    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;339(12):792–798.RCTPMID 9738086PubMed
  15. 15
    Guterman EL, Sanford JK, Betjemann JP, et al. Prehospital midazolam use and outcomes among patients with out-of-hospital status epilepticus. Neurology. 2020;95(24):e3203–e3212.CohortPMID 32943481PMCPubMed
  16. 16
    Navarro V, Dagron C, Elie C, et al. Prehospital treatment with levetiracetam plus clonazepam or placebo plus clonazepam in status epilepticus (SAMUKeppra): a randomised, double-blind, phase 3 trial. Lancet Neurol. 2016;15(1):47–55.RCTPMID 26627366PubMed
  17. 17
    Vossler DG, Bainbridge JL, Boggs JG, et al. Treatment of refractory convulsive status epilepticus: a comprehensive review by the American Epilepsy Society Treatments Committee. Epilepsy Curr. 2020;20(5):245–264.ReviewPMID 32822230PMCPubMed
  18. 18
    Nickson C. Status epilepticus. Critical Care Compendium, Life in the Fast Lane; 2024.FOAMlitfl.comPage read
  19. 19
    Coralic Z, Kapur J, Olson KR, et al. Treatment of toxin-related status epilepticus with levetiracetam, fosphenytoin, or valproate in patients enrolled in the Established Status Epilepticus Treatment Trial. Ann Emerg Med. 2022;80(3):194–202.CohortPMID 35718575PubMed
  20. 20
    Slessor D. ESETT: Randomized trial of three anticonvulsant medications for status epilepticus. The Bottom Line; 2019.FOAMthebottomline.org.ukPage read
  21. 21
    Vignatelli L, Tontini V, Meletti S, et al. Clinical practice guidelines on the management of status epilepticus in adults: a systematic review. Epilepsia. 2024;65(6):1512–1530.Meta-analysisPMID 38606469PubMed
  22. 22
    Dalziel SR, Borland ML, Furyk J, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet. 2019;393(10186):2135–2145.RCTPMID 31005386PubMed
  23. 23
    Lyttle MD, Rainford NEA, Gamble C, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet. 2019;393(10186):2125–2134.RCTPMID 31005385PMCPubMed
How this page was made
  • Written from scratch. No source text was copied; facts are restated and cited.
  • The anchor is the 2024 ACEP clinical policy, whose full text was read from the PDF on acep.org. It answers one question, the choice of second-line drug. The rest of the treatment pathway and all first-line doses come from the 2016 American Epilepsy Society guideline: its full text was read on PubMed Central, and its treatment algorithm chart was read on aesnet.org. No newer AES or Neurocritical Care Society treatment guideline was found. The 2012 Neurocritical Care Society guideline PDF could not be retrieved, so it is not cited.
  • Each PubMed citation was resolved through NCBI E-utilities, and each number was checked against that paper's abstract or open full text. The ICU review by Rossetti and colleagues was read in full on PubMed Central.
  • Doses come only from the AES algorithm, the ACEP dosing table, and FDA labels on DailyMed. No dose is given for anesthetic infusions or intranasal and buccal midazolam, because no guideline text or label read for this page confirmed one.
  • This page covers adults. Pediatric care differs: the AES guideline makes separate recommendations for children, and ConSEPT and EcLiPSE studied children only.
  • Figure 1 was drawn for this page from the AES algorithm. No openly licensed image on Wikimedia Commons showed convulsive status epilepticus suitably, so none is used.
  • Not for clinical use until physician review.
Not for clinical use

AI-generated draft. Not reviewed by a physician. This page is for education only and may contain errors, including in doses. Do not use it to diagnose, treat or make decisions about any patient. Rely on your own clinical judgment, your institution's protocols and current drug labeling. Reading this page does not create a physician-patient relationship. Full terms