Step-wise Antiseizure Drug Sequence for Convulsive Status Epilepticus (Adults)
(Weight-based doses assume ≥ 40 kg; adjust for organ dysfunction, pregnancy, and local protocols.)
1. Emergent (0 – 5 minutes from onset)
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Lorazepam 0.1 mg/kg IV push (maximum 4 mg).
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Give over ~1 minute.
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If convulsions continue after 5 minutes, repeat the same dose once.
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No IV access? Use one of the following instead:
| Route | Medication | Dose (single administration) |
|---|---|---|
| IM | Midazolam | 0.2 mg/kg (maximum 10 mg) |
| IN | Midazolam | 0.2 mg/kg split between nares |
| PR/IV | Diazepam | 0.15 mg/kg (maximum 10 mg) |
2. Urgent / Established (5 – 20 minutes)
Choose one of these second-line antiepileptic drugs and give a full loading dose:
| Drug | Loading dose | Infusion rate & notes |
|---|---|---|
| Fosphenytoin | 20 mg PE/kg IV (max 1 500 mg PE) | ≤ 150 mg PE/min; monitor BP, ECG |
| Valproate | 40 mg/kg IV (max 3 000 mg) | Infuse over ≈10 min; avoid in pregnancy or severe liver disease |
| Levetiracetam | 60 mg/kg IV (max 4 500 mg) | Infuse over ≈10 min; minimal drug–drug interactions |
3. Early Refractory (20 – 40 minutes)
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If seizures persist, give another agent from the urgent step that has not yet been used
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Phenobarbital 15 – 20 mg/kg IV (infuse ≤ 100 mg/min).
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Anticipate need for airway control and vasopressors.
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4. Refractory Status (> 40 – 60 minutes)
Initiate continuous IV anesthetic infusion in the ICU with continuous EEG:
| Agent | Bolus | Maintenance infusion |
|---|---|---|
| Midazolam | 0.2 mg/kg | 0.05 – 2 mg/kg per hour |
| Propofol | 1 – 2 mg/kg | 30 – 200 µg/kg per minute |
| Ketamine | 1 – 3 mg/kg | 1 – 5 mg/kg per hour |
| Pentobarbital | 5 – 15 mg/kg | 0.5 – 5 mg/kg per hour |
Titrate to burst-suppression or seizure cessation on EEG; provide mechanical ventilation and hemodynamic support.
Parallel Supportive Measures
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Airway–Breathing–Circulation
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High-flow O₂; prepare for intubation if persistent seizures or respiratory compromise.
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Rapid bedside checks
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Finger-stick glucose; treat hypoglycaemia immediately if present.
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Consider thiamine 100 mg IV before glucose in malnourished/alcohol-use patients.
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Diagnostics
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Labs: CBC, CMP, magnesium, calcium, antiepileptic levels, toxicology screen.
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Imaging: non-contrast head CT early if first episode or concern for structural lesion.
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LP if infectious cause suspected and imaging safe.
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Identify and correct precipitants
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Electrolyte disturbances, infection, stroke, medication non-adherence, alcohol/benzodiazepine withdrawal, toxin exposure, etc.
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Maintenance therapy
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Start maintenance dosing of chosen AED once seizures controlled (e.g., levetiracetam 1 g IV/PO q12h, adjust for renal function).
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Avoid under-dosing
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Full weight-based boluses are more effective than multiple small “titrations.”
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Key references: American Epilepsy Society “Guideline for Treatment of Convulsive Status Epilepticus” (2020 update); ESETT randomized trial (NEJM, 2019); Neurocritical Care Society recommendations.
Does lacosamide have a place in treating convulsive status epilepticus (CSE)?
Intravenous lacosamide (LCM) is now widely accepted as a reasonable second-line (urgent-phase) option and a useful agent for early refractory cases, alongside fosphenytoin, valproate and levetiracetam.
Where it fits in the sequence
| Phase | Typical choices | How LCM can be used |
|---|---|---|
| Emergent (0–5 min) | Benzodiazepine | Not used |
| Urgent / Established (5–20 min) | One full-dose AED (LEV, VPA, FOS) | LCM 400 mg IV over 5 min is an evidence-supported alternative when: 1) another sodium-channel blocker is preferred to phenytoin, 2) phenytoin/VPA are contraindicated, or 3) the centre’s protocol favours LCM. |
| Early refractory (20–40 min) | Give a different class not yet used, e.g. phenobarbital | If LCM was not the urgent drug, it can be loaded here (8 mg/kg, max 600 mg) before moving to barbiturates or anaesthetic infusions. |
| Refractory (>40 min) | Continuous midazolam, propofol, ketamine, etc. | LCM occasionally added as adjunct if not given earlier. |
Several contemporary ICU protocols list the sequence “LEV → LCM → phenobarbital/valproate” on the grounds of similar efficacy but better haemodynamic tolerance than fosphenytoin. (EMCrit Project)
Efficacy evidence (high-level summary)
| Study type | Key finding |
|---|---|
| Large cohort 2013-2022 comparing LCM, LEV, VPA as second-line therapy (n ≈ 500). | LCM terminated SE in 59 % of episodes—statistically equivalent to LEV and VPA—and was not associated with worse functional outcome or mortality. (PubMed) |
| 2024 network meta-analysis of RCTs on second-line AEDs in adult SE (12 trials, 2 300 pts). | No single agent clearly superior; LCM ranked third for seizure cessation probability, overlapping confidence intervals with the ESETT drugs. (PubMed) |
| Prospective registries & case-series (2012-2023, > 700 episodes) | Mean success 50-65 % with a 400 mg load; hypotension or bradyarrhythmia < 5 %. (PubMed) |
Bottom line: LCM’s effectiveness is comparable to other second-line AEDs, with favourable tolerability.
Practical dosing and monitoring (adult ≥ 40 kg)
| Step | Dose | Notes |
|---|---|---|
| Initial load | 400 mg IV (≈ 5 mg/kg) over 5 minAlternate weight-based: 8 mg/kg (max 600 mg) | Higher loads (> 5 mg/kg) correlate with better seizure control. (EMCrit Project) |
| Re-load if still seizing | 200 mg IV (or 5 mg/kg, max cumulative 600 mg) after 10–15 min | Skip if another urgent drug is planned. |
| Maintenance | 200 mg IV/PO q12 h (range 100–300 mg q12 h) | 1:1 IV ↔ PO; reduce by 25 % if eGFR < 30 ml/min; avoid Child-Pugh C. |
| Monitoring | ECG/telemetry for PR-interval ↑ or AV-block; BP for hypotension | Conduction disease is a relative contraindication. |
Advantages
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Rapid push (≤ 5 min) without propylene glycol, minimal hypotension or respiratory depression.
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Clean PK profile – negligible cytochrome interactions; 100 % oral bioavailability for seamless IV→PO transition.
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Dosing simplicity – fixed 400 mg load fits most adults, avoiding weight calculations at the bedside.
Limitations / cautions
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PR-interval prolongation and rare AV block—obtain baseline ECG in patients with conduction disease.
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Limited paediatric RCT data (though observational results are encouraging).
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Not yet incorporated into the 2020 American Epilepsy Society guideline (published before robust LCM data), so local protocols vary.
Practical take-home
When levetiracetam, valproate or fosphenytoin are unsuitable or have already failed, lacosamide 400 mg IV is a perfectly acceptable second- or third-line agent for convulsive status epilepticus, with efficacy on par with traditional drugs and fewer haemodynamic concerns. Make sure to push it over 5 minutes, keep the cardiac monitor on, and start a 200 mg q12 h maintenance regimen once seizures stop.
5–20 min
(rate ≤ 150 mg PE/min) 1500 mg PE Compatible in NS/D5W;
monitor QTc & BP
renal dose adjust maintenance
20–40 min
Phenobarbital 15–20 mg/kg IV - Infuse phenobarbital ≤ 100 mg/min; anticipate intubation
• Midazolam : bolus 0.2 mg/kg → 0.05–2 mg/kg/h
• Propofol : bolus 1–2 mg/kg → 30–200 µg/kg/min
• Ketamine : bolus 1–3 mg/kg → 1–5 mg/kg/h
• Pentobarbital : bolus 5–15 mg/kg → 0.5–5 mg/kg/h Titrate to burst-suppression on EEG — Requires ICU, continuous EEG, mechanical ventilation, vasopressor readiness
Additional Key Actions (parallel to drug therapy)
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Airway, Breathing, Circulation – position, oxygen, intubate if needed; check bedside glucose and treat hypoglycaemia.
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Diagnostics – finger-stick glucose, ABG, CBC, CMP, antiepileptic drug levels, toxicology screen; consider CT/MRI and LP when indicated.
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Maintenance & Prevention – start maintenance AED (e.g., levetiracetam 1 g q12h) once seizure controlled; identify & treat triggers (infection, stroke, metabolic derangements, medication non-adherence).
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Continuous EEG – begin within 20–30 min if seizures persist or patient paralysed.
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Avoid under-dosing – single adequate weight-based loading is superior to “crescendo” small doses.
Doses and sequence compiled from the American Epilepsy Society guideline, the 2019 ESETT trial, and recent high-quality reviews
Below are pragmatic maintenance-dosing guides for the three antiepileptic drugs most commonly loaded during the urgent phase of convulsive status epilepticus. All doses assume an adult ≥ 40 kg with normal organ function; individualise for age, weight, renal/hepatic status, pregnancy, drug interactions and levels.
1 . Fosphenytoin / Phenytoin (Na⁺-channel blocker)
| Point | Practical details |
|---|---|
| When to start | 4–6 h after the 20 mg PE/kg loading dose or once seizure control is secure and the patient is hemodynamically stable. |
| Typical daily dose | 4–6 mg PE/kg/day divided q8–12 h. Most adults: 300–400 mg PE per day (e.g., 150 mg PE IV/PO q8h or 200 mg PE IV/PO q12h). |
| IV → PO switch | 1 mg phenytoin ≈ 1 mg PE fosphenytoin; the oral form can replace IV milligram-for-milligram. |
| Therapeutic target | Total phenytoin 10–20 µg/mL (free 1–2 µg/mL); draw first level ~24 h after the initial load. |
| Adjustments | Raise or lower by 50–100 mg/day based on trough level and toxicity; use “phenytoin correction” if hypoalbuminaemia or ESRD. |
2 . Valproate (broad-spectrum)
| Point | Practical details |
|---|---|
| When to start | 6 h after the 40 mg/kg load (or sooner if seizures re-emerge). |
| Typical daily dose | 15–60 mg/kg/day divided q8–12 h. Common starting point: 1 g IV/PO q12 h (≈ 30 mg/kg/day for a 70 kg adult). |
| IV ↔ PO | 1:1 conversion; tablets, syrup or sprinkle capsules when enteral route allowed. |
| Therapeutic target | Total VPA 50–100 µg/mL for most; 80–125 µg/mL often used in the ICU for seizure prophylaxis after SE. |
| Adjustments / cautions | Reduce dose by 25–50 % in Child-Pugh B/C or when ammonia rises; avoid in pregnancy or urea-cycle disorders; monitor LFTs and platelets. |
3 . Levetiracetam (SV2A modulator)
| Point | Practical details |
|---|---|
| When to start | 6–8 h after the 60 mg/kg loading dose. |
| Typical daily dose | 20–30 mg/kg/day in two divided doses. Usual adult range: 500–1 500 mg IV/PO q12 h (total 1–3 g/day). Many neuro-ICUs start at 1 g q12 h and titrate up to 1.5 g q12 h if seizures recur. |
| IV ↔ PO | 1:1 conversion; tablets or solution via NG/OG once gut is working. |
| Therapeutic target | No routine serum level needed (relationship to efficacy not well defined), but levels can be measured if absorption or compliance is uncertain. |
| Renal adjustment | Reduce total daily dose by 25 % if CrCl 50–80 mL/min, 50 % if CrCl 30–50, and give q24 h if CrCl < 30 or on CRRT; give a supplemental 250–500 mg after dialysis. |
Practical pearls
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Start maintenance early. Delaying more than 6–8 h after the load risks recurrent seizures.
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Use therapeutic drug monitoring for phenytoin/fosphenytoin (and valproate if high doses or organ dysfunction); not routinely needed for levetiracetam.
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Route matters. All three drugs have reliable IV formulations; levetiracetam and valproate are genuinely 1:1 IV ↔ PO conversions. Fosphenytoin becomes phenytoin orally.
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Check interactions. Phenytoin induces CYP enzymes (may lower other drug levels); valproate inhibits CYP2C9 and UGT (may raise lamotrigine, carbapenem interactions); levetiracetam is essentially interaction-free.
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Always reassess the ongoing need for each AED once the acute episode is over and etiology clarified; many patients can taper to one agent long-term.
These maintenance regimens keep serum concentrations in the therapeutic range while you search for—and treat—the underlying cause of the status epilepticus.
