Status Epilepticus

 Step-wise Antiseizure Drug Sequence for Convulsive Status Epilepticus (Adults)

(Weight-based doses assume ≥ 40 kg; adjust for organ dysfunction, pregnancy, and local protocols.)

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1. Emergent (0 – 5 minutes from onset)

• Lorazepam 0.1 mg/kg IV push (maximum 4 mg).

  • Give over ~1 minute.

  • If convulsions continue after 5 minutes, repeat the same dose once.

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)

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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

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3. Early Refractory (20 – 40 minutes)

• If seizures persist, give another agent from the urgent step that has not yet been used
  or

• Phenobarbital 15 – 20 mg/kg IV (infuse ≤ 100 mg/min).

  • 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.

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Parallel Supportive Measures

1. Airway–Breathing–Circulation

   • High-flow O₂; prepare for intubation if persistent seizures or respiratory compromise.

2. Rapid bedside checks

   • Finger-stick glucose; treat hypoglycaemia immediately if present.

   • Consider thiamine 100 mg IV before glucose in malnourished/alcohol-use patients.

3. Diagnostics

   • Labs: CBC, CMP, magnesium, calcium, antiepileptic levels, toxicology screen.

   • Imaging: non-contrast head CT early if first episode or concern for structural lesion.

   • LP if infectious cause suspected and imaging safe.

4. Identify and correct precipitants

   • Electrolyte disturbances, infection, stroke, medication non-adherence, alcohol/benzodiazepine withdrawal, toxin exposure, etc.

5. Maintenance therapy

   • Start maintenance dosing of chosen AED once seizures controlled (e.g., levetiracetam 1 g IV/PO q12h, adjust for renal function).

6. Avoid under-dosing

   • 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.

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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)

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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.

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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.

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Advantages

• Rapid push (≤ 5 min) without propylene glycol, minimal hypotension or respiratory depression.

• Clean PK profile – negligible cytochrome interactions; 100 % oral bioavailability for seamless IV→PO transition.

• Dosing simplicity – fixed 400 mg load fits most adults, avoiding weight calculations at the bedside.

Limitations / cautions

• PR-interval prolongation and rare AV block—obtain baseline ECG in patients with conduction disease.

• Limited paediatric RCT data (though observational results are encouraging).

• Not yet incorporated into the 2020 American Epilepsy Society guideline (published before robust LCM data), so local protocols vary.

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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.

Urgent
5–20 min

  Fosphenytoin (Na⁺ blocker) 20 mg PE/kg IV
(rate ≤ 150 mg PE/min) 1500 mg PE Compatible in NS/D5W;
monitor QTc & BP 

 Valproate (broad-spectrum) 40 mg/kg IV over 10 min 3000 mg Avoid in pregnancy, severe hepatic disease 

  Levetiracetam (SV2A) 60 mg/kg IV over 10 min 4500 mg Few drug interactions;
renal dose adjust maintenance 

 

Short-Refractory
20–40 min

 If still seizing, give one unused drug from above **or**
Phenobarbital 15–20 mg/kg IV - Infuse phenobarbital ≤ 100 mg/min; anticipate intubation 

Refractory

> 40–60 min 

  Continuous infusions
• 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)

1. Airway, Breathing, Circulation – position, oxygen, intubate if needed; check bedside glucose and treat hypoglycaemia.

2. Diagnostics – finger-stick glucose, ABG, CBC, CMP, antiepileptic drug levels, toxicology screen; consider CT/MRI and LP when indicated.

3. Maintenance & Prevention – start maintenance AED (e.g., levetiracetam 1 g q12h) once seizure controlled; identify & treat triggers (infection, stroke, metabolic derangements, medication non-adherence).

4. Continuous EEG – begin within 20–30 min if seizures persist or patient paralysed.

5. 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.

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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.

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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.

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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.

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Practical pearls

1. Start maintenance early. Delaying more than 6–8 h after the load risks recurrent seizures.

2. Use therapeutic drug monitoring for phenytoin/fosphenytoin (and valproate if high doses or organ dysfunction); not routinely needed for levetiracetam.

3. Route matters. All three drugs have reliable IV formulations; levetiracetam and valproate are genuinely 1:1 IV ↔ PO conversions. Fosphenytoin becomes phenytoin orally.

4. 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.

5. 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.