When to intubate in GCS?

GCS ≤ 8 requires intubation for airway protection. The patient cannot protect their own airway at this level of consciousness. Motor score is the most prognostically important component.

What is the best initial fluid for sepsis resuscitation?

Lactated Ringer's (LR) is the preferred resuscitation fluid. The SMART trial (2018) showed balanced crystalloids reduced death, new renal failure, and persistent renal dysfunction compared to normal saline.

When to start vasopressors in septic shock?

Start norepinephrine (first-line vasopressor) if MAP remains < 65 mmHg after initial 30 mL/kg crystalloid resuscitation, or earlier if patient is profoundly hypotensive. Do not delay pressors to complete full fluid resuscitation.

Why can serum uric acid be normal during acute gout?

During acute inflammation, IL-6 increases renal urate excretion and redistributes urate from plasma to tissues. Up to 40% of acute gout flares have normal serum uric acid. Joint aspiration with polarized microscopy is needed for definitive diagnosis.

How do you distinguish lupus flare from infection in SLE?

Key clues: CRP is low/normal in flare but elevated in infection. Complement (C3/C4) drops in flare but is normal/elevated in infection. Procalcitonin is elevated in bacterial infection but normal in flare. Anti-dsDNA rises in flare, stable in infection.

What is the difference between DKA and HHS?

DKA features acidosis (pH 600), hyperosmolality (> 320), and minimal ketosis -typically in Type 2 DM. DKA requires insulin drip; HHS requires aggressive fluid resuscitation first.

When to give tPA in acute ischemic stroke?

IV alteplase (tPA) can be given within 4.5 hours of last known well time in eligible patients. CT head must rule out hemorrhage first. For large vessel occlusion, mechanical thrombectomy can be performed up to 24 hours with favorable imaging.

What antibiotics for community-acquired pneumonia?

Inpatient non-ICU: ceftriaxone + azithromycin. ICU: ceftriaxone + azithromycin (add vancomycin if MRSA risk). Outpatient healthy: amoxicillin. Outpatient with comorbidities: augmentin + azithromycin or respiratory fluoroquinolone. Duration: 5 days if clinically stable for 48 hours.

How to interpret iron studies?

Iron deficiency: low ferritin (< 30), high TIBC, low iron, low transferrin saturation (< 20%). Anemia of chronic disease: normal/high ferritin (acute phase reactant), low TIBC, low iron. A ferritin of 50-100 in an inflamed patient may still represent iron deficiency.

What is the correction rate for hyponatremia?

Correct sodium no more than 8 mEq/L in 24 hours to avoid osmotic demyelination syndrome (ODS). For symptomatic severe hyponatremia with seizures, give 3% hypertonic saline 100-150 mL bolus over 10-20 minutes. If overcorrected, use D5W + DDAVP rescue protocol.

When to start antibiotics in meningitis?

Within 30-60 minutes. Do NOT delay antibiotics for LP or CT. Draw blood cultures, start empiric antibiotics (vancomycin + ceftriaxone ± ampicillin if > 50 or immunocompromised), then perform LP when possible. Dexamethasone should be given before or with the first antibiotic dose.

DOACs vs warfarin in antiphospholipid syndrome?

DOACs are contraindicated in APS. The TRAPS trial (2018) showed rivaroxaban was inferior to warfarin with more thrombotic events in triple-positive APS patients. Warfarin with INR target 2-3 is the standard for APS, indefinitely.

How to manage scleroderma renal crisis?

ACE inhibitors (captopril) are life-saving -start immediately and titrate aggressively. Do NOT hold for rising creatinine. Steroids > 15 mg prednisone per day precipitate scleroderma renal crisis. ARBs are NOT a substitute -evidence is only for ACEi.

What are the 4 pillars of heart failure treatment?

Guideline-directed medical therapy (GDMT) for HFrEF: (1) ARNI or ACEi/ARB, (2) beta-blocker (carvedilol, metoprolol succinate, or bisoprolol), (3) MRA (spironolactone or eplerenone), (4) SGLT2 inhibitor (dapagliflozin or empagliflozin). All four should be initiated and titrated to target doses.

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EMERGENTICUNeurology

Status Epilepticus

Continuous seizure activity > 5 minutes or ≥ 2 seizures without return to baseline. A neurological emergency -every minute of seizure activity causes irreversible neuronal death. Stop it now.

🔍 Overview

Definitions

Status epilepticus (SE): Seizure ≥ 5 minutes OR ≥ 2 seizures without return to baseline between them.

Refractory SE: Failure of 2 first-line agents (benzodiazepine + second AED) -requires ICU admission and anesthetic agents.

Super-refractory SE: SE persisting ≥ 24 hours after initiation of anesthetic agents, including recurrence on weaning.

Causes

Known epilepsy + subtherapeutic AED levels (most common)
Acute CNS insult: stroke, hemorrhage, encephalitis, meningitis, trauma, tumor
Metabolic: severe hyponatremia, hypoglycemia, hypocalcemia, uremia
Toxins/withdrawal: alcohol withdrawal, cocaine, TCAs, isoniazid
Anoxic brain injury (post-cardiac arrest)
Autoimmune encephalitis (anti-NMDA receptor -especially young women)

Non-Convulsive SE (NCSE)

Don't miss this. NCSE presents as altered mental status, confusion, or subtle motor movements without obvious convulsions. Common after convulsive SE is "treated." Only diagnosed by EEG. Any patient with AMS after a seizure who doesn't wake up → get EEG.

🧪 Workup

Workup, While Treating

Workup happens in parallel with treatment. Never delay benzodiazepine administration to chase labs or imaging.

Fingerstick glucose FIRST, hypoglycemia is a reversible cause of seizure
BMP, Na (hyponatremia), Ca, Mg, renal function
AED levels (if patient on chronic anticonvulsants), subtherapeutic levels are a top cause of breakthrough SE
CBC, leukocytosis (infection, stress)
LFTs, ammonia, hepatic encephalopathy with myoclonus
Toxicology screen, sympathomimetic, cocaine, alcohol withdrawal, TCA overdose, INH toxicity (→ pyridoxine)
Lactate, elevated early post-seizure (anaerobic metabolism); should clear within ~1h if seizure has stopped
Non-contrast CT head, rule out stroke, hemorrhage, mass, edema
LP, if meningitis/encephalitis suspected (fever, immunocompromised, signs of infection)
MRI brain, after acute stabilization; more sensitive for cortical lesions, autoimmune encephalitis
Continuous EEG × 24–48h, mandatory if patient doesn't rapidly return to baseline; diagnoses NCSE (present in up to 30% of persistent coma after convulsive SE)
Pregnancy test, eclampsia is a stroke mimic and changes AED choice (levetiracetam preferred; avoid valproate)
Autoimmune encephalitis panel (anti-NMDA-R, LGI1, GABA-B, etc.), if no clear etiology, especially young women

Post-Ictal LFT Gotcha, AST Is Muscle, Not Liver

Generalized tonic-clonic seizures cause subclinical-to-overt rhabdomyolysis. AST is constitutively present in skeletal muscle and leaks out when fibers lyse during the seizure (it isn't "produced" on demand, just released). ALT is in muscle too but at lower concentration, which is why the post-ictal pattern is AST > ALT, the opposite of viral hepatitis.

Classic post-ictal lab pattern:

↑↑ CK (often 1,000 to >10,000 U/L), confirms muscle source. Always order CK on a post-ictal LFT abnormality.
↑ AST and ↑ ALT, with AST > ALT. AST often 200–500 in moderate post-ictal rhabdo.
↑ LDH, ↑ aldolase (also leaked from muscle)
↑ K⁺, ↑ phosphate, ↓ Ca²⁺ (intracellular contents released; Ca²⁺ binds to damaged muscle and phosphate)
Tea-colored urine, dipstick + for blood with no RBCs on micro = myoglobinuria
AKI from myoglobin cast nephropathy (CK > 10,000 = high risk)

Why it matters: A post-ictal patient with AST 300 / ALT 200 / AST > ALT does not need a hepatitis serology workup. Check CK first. If CK is high, the LFT bump is muscle and trends down with hydration over 3–5 days. Chasing hepatitis B/C, ANA, and ferritin wastes time and money and delays the right intervention, IV fluids targeting UOP 200–300 mL/hr, q4–6h K⁺, watching for compartment syndrome.

One more nuance, myoglobin does NOT cause jaundice. Although myoglobin contains heme, its clinical fate in rhabdo is renal excretion (causing the tea-colored urine and pigment AKI), not conversion to bilirubin. Bilirubin overwhelmingly comes from hemoglobin breakdown by splenic macrophages (~80% of daily production). If a post-ictal or rhabdo patient is jaundiced, look elsewhere, hemolysis, ischemic hepatitis from shock, or drug-induced hepatic injury.

Post-Ictal Lab Timing Reference

Sorted from fastest-decay to slowest, so you know what's still recoverable as a diagnostic clue depending on when the patient hits your ED. Magnitudes are typical for a single GTC seizure; massive seizures or status epilepticus push everything higher.

Lab	Starts to Rise	Peaks	Back to Normal	Typical Magnitude	Why It Matters
Lactate	Within minutes	Immediate post-event	30–90 min	5–15 mmol/L	Best fast discriminator. Rapid clearance distinguishes post-ictal from sepsis (sepsis lactate doesn't drop in an hour). Cutoff: lactate > 2.5 mmol/L within 2h of TLOC has ~80% sensitivity, ~95% specificity for GTC seizure.
Anion gap / pH ↓	Minutes	Immediate	30–90 min	AG often > 16, pH 7.20–7.30	Tracks lactate. Resolves as lactate clears. Don't confuse with DKA or toxic ingestion if it's already correcting.
Prolactin	10–20 min	20 min	60 min	2–3× baseline	GTC vs PNES (psychogenic non-epileptic seizure). Useless if drawn after 60 min or in NCSE/focal/established status. Window matters.
WBC	Minutes (demargination)	1–2 hours	24–48h	12–20K, neutrophil-predominant	Mild leukocytosis is expected post-seizure, not necessarily infection. Don't reflex broad-spectrum antibiotics on WBC alone.
Cortisol	Minutes	30–60 min	2–4h	2–3× baseline	Not used for diagnosis. Explains the leukocytosis (demargination + neutrophilia + lymphopenia).
Glucose	Minutes	30–60 min	1–2h	150–250 mg/dL	Stress hyperglycemia from catecholamine surge. Don't restart insulin sliding scale based on a single post-ictal glucose.
Ammonia	Immediate	< 60 min	2–12h	2–3× ULN	Can falsely flag hepatic encephalopathy in a non-cirrhotic patient. Recheck in 4–6h before treating with lactulose.
Serum myoglobin	1–3h	6–12h	24h	Variable	Clears rapidly via kidney. Urine myoglobin lingers longer (24–48h). Rarely needed if CK is being trended.
Troponin	3–6h	6–12h	24–72h	Usually low-level (< 0.5 ng/mL)	False bump from sympathetic surge / demand ischemia. Don't reflex an ACS workup if seizure history is solid; trend it instead.
AST	6–12h	24–48h	3–5 days	200–500 U/L	Released from lysed muscle, not made by injured liver. AST > ALT (opposite of viral hepatitis).
ALT	6–12h	24–72h	3–7 days	100–300 U/L	Smaller bump than AST because muscle has less ALT. Tracks AST.
CK	2–12h	24–72h	5–7 days	1,000 to > 10,000 U/L	Best late marker. Confirms a convulsive event happened even days after the lactate window has closed. CK > 10,000 = high AKI risk.
Aldolase	6–12h	24–72h	5–7 days	Variable	Tracks CK. Rarely added if CK is already being trended; useful if CK is borderline and you want corroboration.
K⁺ ↑	Hours	12–24h	2–3 days	Up to 6–7 mEq/L in significant rhabdo	Arrhythmia risk window. Recheck q4–6h until trending down. Don't extrapolate from a single normal K⁺ at hour 2.
Phosphate ↑	Hours	12–24h	3–5 days	5–8 mg/dL	From muscle cell lysis. Contributes to hypocalcemia by binding free Ca²⁺.
Calcium ↓	Hours	24–48h (lowest)	1–2 weeks	Often 7–8 mg/dL corrected	Binds to damaged muscle and phosphate. Don't reflexively replace unless symptomatic, rebound hypercalcemia during recovery is common and replacement makes it worse.
Urine dipstick + blood, no RBCs (myoglobinuria)	1–3h	First 24h	24–48h	Tea-colored urine	Classic finding; dipstick heme cross-reacts with myoglobin. Confirms muscle injury source.
Creatinine ↑ (if AKI)	24–72h	3–5 days	Days to weeks	Variable	Pigment cast nephropathy from myoglobin. Severity proportional to peak CK and time to fluids.
LDH	6–12h	24–48h	7–10 days	500–2,000 U/L	Long half-life; persists longest of all post-ictal markers. Useful retrospective clue if a patient presents days later with unclear history.

Key takeaways for clinical use:

Patient arrives within 1 hour of event: draw lactate, prolactin, ABG/VBG with anion gap. The fast-decay markers are still recoverable. After this window they're gone.
Patient arrives 2–6 hours later: lactate window may be missed. Pivot to early CK trend, troponin (with caveats), early AST/ALT, ammonia.
Patient arrives 24–72 hours later: CK is the workhorse. AST > ALT pattern still visible. LDH still elevated. Lactate and prolactin gone.
Patient arrives 3–7 days later: CK still mildly up, LDH still elevated, urine has cleared. Diagnostic certainty drops; lean on history, EEG, MRI.

Why Bilirubin Isn't on the Post-Ictal List

Despite myoglobin containing heme, post-ictal bilirubin is almost always normal. The myoglobin → heme oxygenase → biliverdin → bilirubin pathway is biochemically real but clinically negligible because myoglobin is renally excreted before metabolism. Bilirubin overwhelmingly comes from hemoglobin breakdown by splenic macrophages (~80% of daily production), and seizures don't cause hemolysis.

If a post-ictal patient IS jaundiced, look elsewhere:

Massive rhabdo (CK > 50,000): mild indirect ↑ (1–3 mg/dL) from heme-load overwhelming conjugation. Uncommon outside truly massive injury.
Status epilepticus + shock → ischemic hepatitis ("shock liver"): direct or mixed ↑, AST in the thousands, LDH ↑↑↑, ↑ INR. Peaks 24–72h, falls fast once perfusion is restored.
AED-induced liver injury (DILI): direct ↑ with AST/ALT, often weeks after starting the drug. Valproate, lamotrigine, phenytoin are the usual suspects.
DRESS (drug-induced hypersensitivity): direct ↑ + eosinophilia + rash + fever. Carbamazepine, phenytoin, lamotrigine, days-to-weeks after initiation.
Underlying alcohol use or cirrhosis: bilirubin reflects baseline liver disease, not the seizure. Common in withdrawal-related seizures.
Hemolysis (any cause): haptoglobin ↓, retic ↑, schistocytes or spherocytes on smear.

Practical workup if post-ictal patient is jaundiced: CBC + smear + retic + haptoglobin (hemolysis), AST/ALT/INR/LDH trajectory (ischemic hepatitis), AED levels + medication review (DILI/DRESS), RUQ ultrasound if direct + alk phos predominant (obstruction).

Did a Seizure Actually Happen? Discriminator Table

When the event isn't witnessed or the story is fuzzy (post-ictal patient can't tell you what happened), these markers separate GTC seizure from syncope from PNES.

Feature	GTC Seizure	Syncope	PNES (psychogenic)
Lactate (early, < 1h)	↑↑ (often > 5 mmol/L) then rapid clearance	Normal or trivial bump	Normal
CK at 24h	Often > 1,000 U/L	Normal	Normal (rare exceptions in prolonged events)
Prolactin (drawn 10–60 min post)	2–3× baseline	Mild ↑ at most	Normal
Lateral tongue bite	~99% specific when present (sensitivity ~24%)	No	No
Postictal confusion	> 5 min, gradual recovery	< 30 sec, rapid full recovery	Variable, often abrupt return to baseline
Eyes during event	Open, often deviated	Open or closed	Often forcibly closed (resists examiner opening them)
Cyanosis	Common during tonic phase	Pallor more typical	Absent
Incontinence	Common (urinary > fecal)	Possible if prolonged	Possible (less specific than once thought)

🚨 Management

Status Epilepticus Protocol -Time Is Neurons

0–5 Minutes -Stabilize

ABCs, O₂, IV access, cardiac monitor. POC glucose STAT. If hypoglycemic → D50W (50% dextrose) 50 mL IV (= 25 g dextrose). Give thiamine 100 mg IV before or with dextrose if alcohol use, malnutrition, or unknown history (Wernicke prevention; alcohol withdrawal is a common SE precipitant). Check temperature (fever → active cooling, hyperthermia worsens neuronal injury). Place patient safely, do NOT restrain or put anything in mouth.

5 Minutes -Phase 1: Benzodiazepine (First-Line)

IV access available: Lorazepam (Ativan) 0.1 mg/kg IV (max 4 mg per dose), repeat × 1 in 5 min if no response (max total 8 mg). Alternative: Diazepam (Valium) 0.15–0.2 mg/kg IV (max 10 mg per dose), repeat × 1.
No IV access: Midazolam (Versed) 10 mg IM if ≥ 40 kg (5 mg IM if 13–40 kg). IM is as fast as IV, do not delay for IV access.

RAMPART 2012: IM midazolam = IV lorazepam in efficacy. Use IM if no IV. Why benzos first: they enhance GABAergic inhibition, the same neurotransmission that fails as SE persists (GABA-A receptors internalize, NMDA receptors externalize after ~30 min, which is why benzos lose potency in prolonged SE and you need NMDA antagonists like ketamine).

20 Minutes -Phase 2: Second AED (if benzo fails)

Give ONE of:

Levetiracetam (Keppra) 60 mg/kg IV (max 4500 mg) over 10 min, preferred (fewest drug interactions, no respiratory depression, no cardiac monitoring needed)
Valproate (Depakote) 40 mg/kg IV (max 3000 mg) over 10 min. Avoid in pregnancy (teratogenic, FDA black box), severe liver disease, mitochondrial disease (POLG mutations).
Fosphenytoin (Cerebyx) 20 mg PE/kg IV (max 1500 mg PE), infusion rate ≤ 150 mg PE/min. Cardiac monitoring required (hypotension, arrhythmia during infusion). Use caution in severe liver disease (monitor free phenytoin levels), but not absolutely contraindicated in emergent SE. (Why fosphenytoin, not phenytoin: 3× faster infusion (150 vs 50 mg/min), no purple-glove tissue necrosis on extravasation, less propylene-glycol cardiotoxicity, IM option if IV is lost. Same active drug after 8–15 min plasma hydrolysis.)
Lacosamide (Vimpat) 200–400 mg IV load over 5–15 min, then 100–200 mg IV/PO BID. ALTERNATIVE Not studied in ESETT, but increasingly used when LEV/VPA/PHT are contraindicated or fail. Especially useful in focal-onset SE, hepatic disease (no liver concern), or when minimal drug interactions are needed (no CYP effect, compatible with chemo, immunosuppressants, DOACs, OCPs). Watch for PR prolongation, get baseline ECG; avoid in 2°/3° AV block.

ESETT 2019: all three equally effective (~50% seizure termination at 60 min). Choice is driven by patient factors (pregnancy, liver disease, cardiac comorbidities, drug interactions). Lacosamide is an off-label fourth option supported by post-ESETT consensus and observational data.

40 Minutes -Phase 3: Refractory SE → ICU + Anesthetic

Intubate + continuous EEG. Target burst suppression for 24–48h, then slowly wean.
Options:

Propofol (Diprivan) 1–2 mg/kg IV bolus then 1–15 mg/kg/hr drip. Watch for propofol infusion syndrome (PRIS) (rare but lethal mitochondrial toxicity from prolonged high-dose propofol, impaired fatty-acid β-oxidation → energy failure) at > 5 mg/kg/hr for > 48h: lactic acidosis, rhabdo, hypertriglyceridemia, bradyarrhythmia, cardiac collapse. Cap dose if you can or rotate to midazolam.
Midazolam (Versed) 0.2 mg/kg IV bolus then 0.05–2 mg/kg/hr drip. Tachyphylaxis develops over hours-days; expect dose escalation.
Ketamine (Ketalar) 1–2 mg/kg IV bolus then 1.2–5 mg/kg/hr. NMDA antagonist (the receptor that's externalized in prolonged SE), neuroprotective, preserves hemodynamics, bronchodilator. Increasingly used early in refractory SE.
Pentobarbital (super-refractory): 5 mg/kg bolus then 1–5 mg/kg/hr. Reserve for failure of midazolam/propofol/ketamine; high hemodynamic and infectious complication burden.

Neurology and/or epilepsy consult. Continuous EEG mandatory to detect NCSE and guide treatment (clinical exam useless once paralyzed/sedated).

Concurrent -Find the Cause

CT head (hemorrhage, structural lesion), LP (meningitis/encephalitis -unless ICP elevated), metabolic panel, AED levels, toxicology screen, anti-NMDA/LGI1 antibodies if young woman with encephalopathy, EEG (NCSE).

💊 Medications & Doses

Medications Reference

Drug	Dose	Phase	Notes
Lorazepam (Ativan) 1ST LINE	0.1 mg/kg IV, max 4 mg per dose; repeat × 1 (max 8 mg total)	Phase 1 (IV)	First-line if IV access. Respiratory depression risk -have bag-mask ready. Alternative IV benzo: diazepam (Valium) 0.15–0.2 mg/kg IV, max 10 mg/dose, repeat × 1.
Midazolam (Versed) IM	10 mg IM (> 40 kg); 5 mg (13–40 kg)	Phase 1 (no IV)	RAMPART 2012: non-inferior to IV lorazepam. Faster than establishing IV access. Use the outer thigh.
Levetiracetam (Keppra) PREFERRED 2ND	60 mg/kg IV, max 4500 mg over 10 min	Phase 2	Preferred second agent. No hepatotoxicity, no CYP interactions, no cardiac monitoring needed. Can cause agitation.
Valproate (Depakote) 2ND LINE	40 mg/kg IV, max 3000 mg over 10 min	Phase 2	Avoid: liver disease, pregnancy, metabolic disorders (mitochondrial disease). Effective for absence/myoclonic SE.
Fosphenytoin (Cerebyx) 2ND LINE	20 mg PE/kg IV, max 1500 mg PE	Phase 2	Cardiac monitoring required (hypotension, arrhythmia during infusion). Give ≤ 150 mg PE/min. Use caution in severe liver disease (monitor free phenytoin levels), but not absolutely contraindicated in emergent SE.
Lacosamide (Vimpat) ALTERNATIVE	200–400 mg IV load over 5–15 min, then 100–200 mg IV/PO BID	Phase 2 (off-label SE)	Not in ESETT but increasingly used. Minimal drug interactions, no CYP effect, no respiratory depression, 1:1 IV→PO. PR prolongation, baseline ECG; avoid in 2°/3° AV block. Especially useful in focal SE, hepatic disease, or when LEV/VPA/PHT contraindicated.
Propofol (Diprivan)	2 mg/kg bolus, then 1–15 mg/kg/hr	Phase 3 (refractory)	Rapid, titratable. Propofol infusion syndrome risk at high doses/prolonged use. Requires intubation.
Ketamine (Ketalar)	1.5 mg/kg IV bolus, then 1.2–5 mg/kg/hr	Phase 3	NMDA antagonist. Emerging evidence for refractory SE. Bronchodilator. Preserves airway reflexes better. Less hemodynamic compromise.

Discharge & Outpatient AED Regimen

Acute SE termination buys you the moment; a take-home AED keeps the patient out of the next ED visit. Selection is driven by seizure type, comorbidities, pregnancy status, and interaction profile.

Step 1, Do They Even Need an AED?

Not every seizure patient needs a chronic AED. The decision rests on recurrence risk over the next 2 years.

Provoked seizure (alcohol withdrawal, hypoglycemia, hyponatremia, drug toxicity, fever in pediatrics): treat the cause, no chronic AED. Recurrence rate is low if the trigger is removed.
First unprovoked seizure with high-risk features (abnormal EEG with epileptiform discharges, MRI lesion, status presentation, prior brain insult): ~60% recurrence over 2 years → start AED. Why: the recurrence risk approximates the definition of epilepsy itself, so treatment is justified after a single event.
First unprovoked seizure, normal EEG/MRI, no prior brain insult: ~30% recurrence over 2 years → shared decision. Treating cuts recurrence by ~35%, but does not change long-term remission rate. Many neurologists hold back unless a second seizure occurs (the textbook definition of epilepsy).
Two or more unprovoked seizures (= epilepsy): AED indicated regardless of EEG/MRI.

Step 2, AED Selection by Seizure Type

First-line choice depends on whether the seizures are focal (start in one brain region) or generalized (involve both hemispheres from onset). Ordered most-to-least common in adults.

Seizure Type	First-Line	Alternatives	Avoid (can worsen)
Focal-onset (most common in adults)	Levetiracetam (Keppra), lamotrigine (Lamictal)	Lacosamide (Vimpat), oxcarbazepine (Trileptal), carbamazepine (Tegretol), zonisamide (Zonegran), brivaracetam (Briviact)	—
Generalized tonic-clonic (idiopathic generalized epilepsy)	Levetiracetam, lamotrigine, valproate (Depakote) (if not pregnancy)	Topiramate (Topamax), zonisamide	CBZ, oxcarbazepine, phenytoin, gabapentin, can paradoxically worsen idiopathic generalized epilepsy
Absence (childhood, brief staring spells)	Ethosuximide (Zarontin), valproate	Lamotrigine	CBZ, phenytoin, oxcarbazepine, worsen absence seizures
Myoclonic (juvenile myoclonic epilepsy, JME)	Levetiracetam, valproate	Topiramate, zonisamide, clobazam (Onfi)	CBZ, phenytoin, lamotrigine, oxcarbazepine, gabapentin, can worsen myoclonus

Key principle: if you don't know whether seizures are focal or generalized, default to a broad-spectrum agent (levetiracetam, lamotrigine, valproate, topiramate, zonisamide). Narrow-spectrum drugs (CBZ, phenytoin, gabapentin) can worsen idiopathic generalized epilepsy and should not be empirically chosen.

Step 3, Maintenance Dosing Reference

Drug	Maintenance Dose	Titration / Levels	Key Side Effects & Why It Matters
Levetiracetam (Keppra) FIRST-LINE	500–1500 mg BID PO/IV	Start 500 mg BID, titrate q1–2 wk. No level monitoring needed routinely.	Rare but life-threatening (STOP drug): SJS-like reactions, angioedema, severe thrombocytopenia. Suicidal ideation (AED class effect, FDA warning), screen for new mood changes. Behavioral SE (irritability, anxiety, depression, aggression, rarely psychosis) in ~10–15%, dose-limiting. Empirical pyridoxine (B6) 50–200 mg/day may help in ~30–50% (mechanism unclear, not repleting a true deficiency, supraphysiologic adjunct); switch to brivaracetam if no response in 2–4 weeks. Common but tolerable: somnolence/fatigue ~15%, headache, dizziness, asthenia. Renally cleared, dose-adjust for CrCl < 80.
Lamotrigine (Lamictal) FIRST-LINE	100–200 mg BID	Start 25 mg/day × 2 wk → 50 mg/day × 2 wk → titrate to target over 4–6 wk.	Stevens-Johnson syndrome / TEN if titrated too fast (especially with VPA, which doubles lamotrigine levels, halve the starting dose). Hemophagocytic lymphohistiocytosis (HLH, FDA 2018 boxed warning), fever + cytopenias + ↑ ferritin + ↑ triglycerides → STOP. DRESS, aseptic meningitis (rare). Suicidal ideation (class). Rash distinction: benign maculopapular rash ~10% (days 5–14 of titration); STOP if fever, mucosal involvement, blisters, or desquamation. Common: insomnia, headache, dizziness, ataxia, diplopia, blurred vision. Estrogen-containing OCPs ↓ lamotrigine ~50% during active pill weeks (cycling toxicity risk).
Lacosamide (Vimpat)	100–200 mg BID PO/IV	Start 50 mg BID × 1 wk → 100 mg BID. 1:1 IV-to-PO conversion.	PR prolongation (baseline ECG; avoid in 2°/3° AV block). Rare but serious: DRESS, atrial fibrillation/flutter, syncope. Suicidal ideation (class effect). Common: dizziness, diplopia, ataxia, headache, nausea (slow titration mitigates). Renal dose adjust for CrCl < 30 (cap 300 mg/day). Minimal drug interactions, attractive in polypharmacy.
Oxcarbazepine (Trileptal)	300–1200 mg BID	Start 150 mg BID, titrate weekly.	SJS / DRESS / agranulocytosis (rare; *HLA-B1502 testing in Asian patients, cross-reactive with CBZ). Hyponatremia** in ~25% (SIADH-like, dose-dependent, more in elderly), check Na 1–2 wk after start and after dose increases. Suicidal ideation (class). Mild CYP3A4 inducer at higher doses (still ↓ OCPs, less than CBZ). Common: dizziness, somnolence, diplopia, ataxia, nausea, rash ~5% (less than CBZ).
Carbamazepine (Tegretol)	200–600 mg BID	Start 200 mg BID. Level: 4–12 mcg/mL. Auto-induces own metabolism over 4–6 wk, levels drop after starting.	SJS/TEN, DRESS (HLA-B1502 testing in Asian patients, FDA mandate). Agranulocytosis, aplastic anemia* (rare, monitor CBC q3–6 mo); leukopenia ~10% (usually benign). Hepatotoxicity. Avoid in idiopathic generalized epilepsy (worsens absence/myoclonic). Fetal anomalies (NTDs ~1%, craniofacial, IUGR, FDA category D). SIADH / hyponatremia. Strong CYP3A4/2C9 inducer, drops OCPs, warfarin, DOACs, immunosuppressants, lamotrigine. Common CNS (peak-level dependent): ataxia, nystagmus, diplopia, blurred vision.
Valproate (Depakote ER)	500–1500 mg QD (ER) or 250–750 mg BID (IR)	Level: 50–100 mcg/mL. Check baseline LFTs, recheck if symptomatic.	Hepatotoxicity (especially < 2 yr, mitochondrial disease/POLG mutations, can be fatal). Pancreatitis (rare but fatal, check lipase if abdominal pain). Avoid in pregnancy (NTDs ~1–2%, lower offspring IQ ~9 points, FDA black box). Hyperammonemic encephalopathy can occur with normal LFTs and therapeutic VPA level (treat with L-carnitine). Carbapenem interaction drops VPA > 60% in 24h → breakthrough seizures (do not co-administer). PCOS / menstrual irregularity in adolescent girls. Common: thrombocytopenia, weight gain, alopecia, tremor.
Topiramate (Topamax)	100–200 mg BID	Start 25 mg QHS, titrate by 25–50 mg/wk.	Acute angle-closure glaucoma (FDA warning, typically first month, painful red eye + acute visual change → STOP and ophthalmology emergent). Cleft palate in pregnancy (FDA category D). Suicidal ideation, depression, mood changes. Word-finding difficulty / cognitive slowing (dose-limiting). Kidney stones, metabolic acidosis (non-AG, carbonic anhydrase inhibition), oligohidrosis. Reduced OCP efficacy at > 200 mg/day. Common: paresthesias ~50%, weight loss (helpful or harmful).
Phenytoin (Dilantin)	300 mg QD or 100 mg TID	Level: 10–20 mcg/mL total, 1–2 mcg/mL free. Saturable kinetics, small dose changes cause big level swings.	DRESS, SJS, lupus-like syndrome, lymphadenopathy (rare, life-threatening). Purple glove syndrome from IV extravasation (skin necrosis; use fosphenytoin instead). Fetal hydantoin syndrome (cleft lip/palate, IUGR, microcephaly, distal phalangeal hypoplasia). Cerebellar atrophy from chronic toxicity (sometimes irreversible). Megaloblastic anemia from folate inhibition. Strong CYP inducer (drops OCPs, warfarin, DOACs, immunosuppressants). Common: gingival hyperplasia, hirsutism, coarse facies, ataxia, nystagmus (peak-related), peripheral neuropathy, osteopenia (long-term, vit D catabolism). Free phenytoin levels in low albumin or uremia. Largely supplanted by Keppra/lamotrigine for chronic use.
Zonisamide (Zonegran)	200–400 mg QD	Start 100 mg QD × 2 wk, titrate.	Sulfa allergy = absolute contraindication. Rare but serious: SJS/TEN, DRESS, blood dyscrasias. Suicidal ideation, depression. Oligohidrosis → heat stroke (especially in pediatrics, fatalities reported). Kidney stones, metabolic acidosis (carbonic anhydrase inhibition). Common: cognitive slowing, paresthesias, somnolence, dizziness, anorexia. Long half-life (~60h), once-daily dosing convenient.
Brivaracetam (Briviact)	50–100 mg BID PO/IV	Start 50 mg BID, can titrate quickly.	Rare but serious: anaphylaxis, angioedema, bronchospasm. Suicidal ideation (class). Similar to Keppra (binds same SV2A target with higher affinity) but fewer behavioral side effects, useful when a patient cannot tolerate Keppra-induced irritability/depression. Common: somnolence ~15%, dizziness, fatigue, nausea.

Step 4, Special Populations

Pregnancy / women of childbearing age:

Preferred: lamotrigine or levetiracetam (lowest teratogenic risk in registries; major malformation rates ~2–3%, similar to baseline population).
Avoid: valproate (NTDs ~1–2%, lower offspring IQ ~9 points, FDA black box), topiramate (cleft lip/palate ~1–2%), phenobarbital, polytherapy (additive risk).
Folic acid 4 mg daily at least 3 months before conception (vs 0.4–0.8 mg in general population). Why: AEDs deplete folate, and high-dose folate cuts NTD risk in this population.
OCP interactions: enzyme inducers (CBZ, phenytoin, phenobarbital, oxcarbazepine, topiramate > 200 mg/day) ↓ ethinyl estradiol levels by 30–50% → contraception failure. Use IUD, depot medroxyprogesterone, or higher-dose OCP. Conversely, estrogen ↓ lamotrigine ~50% during active pill weeks.
Levels during pregnancy: volume of distribution and clearance increase. Lamotrigine and levetiracetam levels often drop 30–50% by third trimester, anticipate dose increases. Recheck levels q month and post-partum (taper back).

Elderly: levetiracetam or lamotrigine preferred. Lower interaction burden, less cognitive impact than CBZ/phenytoin/phenobarbital, no induction of warfarin/DOAC metabolism. Start at half the usual dose; renal clearance and protein binding both decline with age.

CKD: lacosamide (low renal clearance), lamotrigine (hepatic clearance), valproate (hepatic). Levetiracetam needs dose reduction (CrCl-based, drops to half-dose at CrCl < 50 and quarter-dose at CrCl < 30).

Hepatic impairment: levetiracetam preferred (renal clearance). Avoid valproate (hepatotoxic), phenytoin (hepatic metabolism + altered protein binding), CBZ (hepatic + induction risk).

Step 5, Discharge Counseling Checklist

Don't skip these conversations, document each one:

Driving restrictions: state-specific. Most US states require 3–6 months seizure-free before driving; some mandate physician reporting (CA, DE, NJ, NV, OR, PA), others rely on patient self-reporting. Document the conversation in the chart, this is a med-legal flashpoint.
Adherence is the #1 cause of breakthrough seizures and SE. Pillbox, smartphone reminders, family involvement. Missed doses are NOT benign, AED levels can drop below threshold within 24–48h.
Triggers to avoid: sleep deprivation (single biggest after non-adherence), alcohol (especially binge → withdrawal seizures), recreational drugs, photic stimulation (in photosensitive epilepsy, ~5% of patients).
Bone health: long-term enzyme inducers (CBZ, phenytoin, phenobarbital, primidone) increase osteoporosis risk via vitamin D catabolism. DEXA every 2 years after 5+ years of therapy; vitamin D 1000–2000 IU + calcium 1000–1200 mg daily.
SUDEP counseling: sudden unexpected death in epilepsy occurs ~1 per 1000 patient-years, higher with uncontrolled GTC seizures. Best prevention is seizure freedom. Discuss bedside monitors, partner education, prone-sleep avoidance in high-risk patients.
Follow-up: neurology in 1–2 weeks, EEG (if not done), MRI brain (if not done). Recheck AED level at 1–2 weeks for narrow-TI drugs (phenytoin, valproate, CBZ).
Pregnancy planning: if patient is or could become pregnant, discuss preferred AEDs and high-dose folic acid before conception, not after.

Step 6, Drug-Drug Interactions to Watch

🚫 Carbapenem × valproate: meropenem, imipenem, ertapenem drop VPA serum levels by 60–100% within 24 hours, breakthrough seizures or SE even in well-controlled patients. Do not co-administer. Bridge to levetiracetam if a carbapenem is essential.

Enzyme inducers (CBZ, phenytoin, phenobarbital, primidone, oxcarbazepine, topiramate at > 200 mg/day) ↓ levels of:

OCPs and emergency contraception (~30–50% drop in ethinyl estradiol) → contraception failure. Use IUD or depot medroxyprogesterone.
Warfarin and DOACs → subtherapeutic anticoagulation, thrombotic events.
Immunosuppressants (cyclosporine, tacrolimus, sirolimus) → graft rejection risk.
Direct-acting antivirals (HCV regimens) → treatment failure.
Methadone, buprenorphine → withdrawal symptoms, cravings.

Lamotrigine × valproate: VPA inhibits glucuronidation, doubles lamotrigine half-life. Halve the lamotrigine starting dose and titrate even more slowly to avoid SJS/TEN.

Valproate as an inhibitor (raises other drug levels): VPA inhibits glucuronidation and CYP2C9, raising phenobarbital levels (sedation, respiratory depression risk) and warfarin levels (bleeding risk; recheck INR after starting/stopping VPA). Conversely, enzyme inducers (phenytoin, carbamazepine, phenobarbital, rifampin) lower VPA levels and can cause breakthrough seizures, recheck VPA level if any of these is started.

Lamotrigine × estrogen-containing OCPs: estrogen induces lamotrigine glucuronidation, level drops ~50% during the 3-week active pill phase, then rebounds during placebo week (toxicity risk). Adjust dose with cyclic OCP, or switch to continuous-cycle / progesterone-only contraception.

📋 On Rounds

On Rounds

📋 Sample Presentation

"Mr. Abreu is a 34-year-old with known epilepsy who was brought in with generalized tonic-clonic seizure activity for approximately 12 minutes prior to EMS arrival. He received midazolam 10 mg IM en route with partial response. In the ED he received lorazepam 4 mg IV -the seizure terminated after 3 minutes. He was then loaded with levetiracetam 60 mg/kg IV. His home levetiracetam level was undetectable -consistent with medication non-adherence as the precipitant. CT head is negative. He is currently post-ictal but following commands. EEG is monitoring for non-convulsive status. Neurology is following."

Pimp Questions

Why 5 minutes as the definition of status epilepticus?

Most self-limited seizures stop within 2–3 minutes. Beyond 5 minutes, spontaneous termination becomes unlikely AND neuronal injury from excitotoxicity begins. At 30 minutes, permanent injury is near certain. The operational definition was lowered from 30 to 5 minutes to encourage earlier intervention.

What is the preferred second-line AED and what trial established this?

All three agents are equally effective ESETT 2019 -approximately 50% success at 60 minutes. Levetiracetam is generally preferred due to favorable safety profile: no cardiac monitoring, no hepatotoxicity, fewer drug interactions.

A patient's seizures stopped but they haven't woken up. How long do you wait before worrying?

Post-ictal state typically resolves within 30-60 minutes. If the patient hasn't returned to baseline by 60 min → concern for non-convulsive status epilepticus (NCSE). NCSE = ongoing seizure activity on EEG without visible convulsions -the brain is still seizing but the body isn't moving. This occurs in up to 48% of patients after convulsive status. Get an EEG immediately if there's persistent AMS after apparent seizure cessation.

What is the correct sequence of medications in status epilepticus?

Stage 1 (0-5 min): Benzodiazepine -lorazepam 0.1 mg/kg IV (max 4 mg/dose, repeat × 1) OR midazolam 10 mg IM if no IV access. Stage 2 (5-20 min, BZD failed): Second-line AED -levetiracetam 60 mg/kg IV (max 4500 mg) OR fosphenytoin 20 mg PE/kg IV OR valproate 40 mg/kg IV. These are considered equivalent per ESETT, 2019 trial -choose based on patient factors (valproate: avoid in pregnancy/liver disease; fosphenytoin: avoid in heart block).

Clinical Examples

📋 Case 1, Convulsive SE from Non-Adherence

Patient: 28M with epilepsy on levetiracetam. Found seizing ~10 min ago. GTC activity ongoing on EMS arrival.

Key findings: No IV access initially. Glucose 110. Levetiracetam level undetectable.

Management:

Midazolam (Versed) 10 mg IM if ≥ 40 kg (5 mg if 13–40 kg), no IV needed. RAMPART, 2012
Establish IV; if seizure persists, levetiracetam (Keppra) 60 mg/kg IV (max 4500 mg) over 10 min
Check BMP (Na, Ca, Mg), tox screen, AED levels, CT head
Continuous EEG if not at baseline within 30–60 min (rule out NCSE)

Teaching point: Medication non-adherence is the most common cause of SE. IM midazolam is non-inferior to IV lorazepam and faster when IV access is unavailable.

📋 Case 2, Refractory SE Requiring Intubation

Patient: 52F with brain metastases. Seizing 25 min despite lorazepam (Ativan) 4 mg IV × 2 and levetiracetam (Keppra) 4500 mg IV.

Key findings: Failed first-line and second-line agents = refractory SE. SpO₂ 88%.

Management:

Intubate for airway protection
Propofol (Diprivan) 1–2 mg/kg bolus then 1–15 mg/kg/hr, titrate to burst suppression on cEEG. Watch for propofol infusion syndrome (PRIS) at > 5 mg/kg/hr × 48h.
Alternative: midazolam (Versed) 0.2 mg/kg bolus then 0.05–2 mg/kg/hr, or ketamine (Ketalar) 1–2 mg/kg bolus then 1.2–5 mg/kg/hr (NMDA antagonist, preserves hemodynamics, increasingly used early)
Continuous EEG mandatory, clinical exam useless once sedated
Target burst suppression 24–48h, then slowly wean
MRI brain; neurosurgery and oncology consult

Teaching point: After second-line AED fails = refractory SE. Must have cEEG, cannot assess seizure activity clinically in sedated patients. ESETT, 2019 showed all three second-line AEDs equally effective (~50% cessation).

📋 Case 3, Non-Convulsive SE (NCSE)

Patient: 74M post-cardiac arrest with ROSC. Comatose at 24h. Subtle eye twitching and lip movements. No overt convulsions.

Key findings: Continuous EEG: electrographic seizures without motor correlate. NCSE in up to 30% of comatose ICU patients.

Management:

IV levetiracetam (Keppra) 60 mg/kg (less sedating, preferred post-arrest)
If seizures persist, add lacosamide (Vimpat) 200 mg IV or valproate (Depakote) 40 mg/kg IV (max 3000 mg)
Avoid overly aggressive sedation unless electrographic SE persists
Continue targeted temperature management per post-arrest protocol
Neurology consult for EEG interpretation

Teaching point: NCSE is extremely common and frequently missed. Any ICU patient with unexplained AMS or failure to wake up post-seizure needs an EEG. You cannot diagnose NCSE without EEG.

Monitoring

Continuous EEG
AED levels
Neuro exam q2-4h
Glucose
CK if prolonged seizure

⚡ Summary

Summary

Definition

Seizure ≥ 5 min OR ≥ 2 seizures without return to baseline. Every minute = neuronal death.

Phase 1 (0–20 min)

Lorazepam 0.1 mg/kg IV OR midazolam 10 mg IM (no IV access). Check glucose first.

Phase 2 (20–40 min)

Levetiracetam 60 mg/kg IV (preferred), valproate 40 mg/kg, or fosphenytoin 20 mg PE/kg. All equal ESETT 2019.

Phase 3 (refractory)

Intubate + continuous EEG. Propofol or midazolam infusion. Neurology consult. Find the cause.

Don't Miss

Non-convulsive SE -AMS after seizure + no waking up = EEG immediately.

Cause Hunt

AED levels, glucose, lytes, CT head, LP (if no ICP), toxicology. Anti-NMDA antibodies in young women with encephalopathy.

📄 One Pager

ICU · Neurology · One Pager

Status Epilepticus

Every minute of seizure = neuronal death. Three phases. Benzo first. Levetiracetam second. Intubate + EEG if refractory. Don't miss NCSE.

⏱️ 3-Phase Protocol

Immediately: ABCs, glucose, IV access, O₂, monitor. Thiamine before glucose.

0–20 min -Benzo: Lorazepam 0.1 mg/kg IV (max 4 mg) OR midazolam 10 mg IM if no IV RAMPART 2012

20–40 min -2nd AED: Levetiracetam 60 mg/kg IV (preferred) OR valproate 40 mg/kg OR fosphenytoin 20 mg PE/kg -all equal ESETT 2019

> 40 min -Refractory: Intubate + continuous EEG + propofol or midazolam infusion. Neurology consult.

💊 Phase 2 Drugs

Levetiracetam60 mg/kg IV (preferred)

Valproate40 mg/kg IV

Fosphenytoin20 mg PE/kg IV

🔍 Find the Cause

AED levels (non-adherence)
Glucose, electrolytes
CT head → LP
Toxicology screen
Anti-NMDA antibodies

⚠️ Don't Miss

NCSE -AMS after seizure + not waking → EEG now
Glucose before anything else
Thiamine before glucose in alcoholic