Sepsis Definitions

Classic (1991/2001 “Sepsis-2”) Definitions

Stage	Diagnostic Criteria
Sepsis	Suspected or proven infection plus ≥ 2 SIRS criteria: Temp > 38 °C or < 36 °C HR > 90 beats min-1 RR > 20 min-1 or PaCO₂ < 32 mm Hg WBC > 12 × 109/L, < 4 × 109/L, or > 10 % bands
Severe Sepsis	Sepsis plus acute organ dysfunction, hypoperfusion, or hypotension. Typical examples: lactate > 2 mmol L-1; SBP < 90 mm Hg or MAP < 70; Cr ≥ 2 mg dL-1 or UO < 0.5 mL kg-1 h-1; bili ≥ 2 mg dL-1; platelets < 100 × 109/L; INR > 1.5; PaO₂/FiO₂ ≤ 300.
Septic Shock	Severe sepsis with persistent arterial hypotension despite adequate fluid resuscitation (conventionally ≥ 30 mL kg crystalloids) and requiring vasopressors.

Modern (2016 “Sepsis-3”) Definitions

Stage	Diagnostic Criteria
Sepsis	Suspected or documented infection plus acute organ dysfunction, quantified as an increase in SOFA score ≥ 2 points from baseline. (Outside the ICU, a quick screen — qSOFA ≥ 2: altered mentation, RR ≥ 22, SBP ≤ 100 mm Hg — signals need for full SOFA work-up.)
Septic Shock	Sepsis with both: 1) Vasopressor-dependent hypotension to maintain MAP ≥ 65 mm Hg and 2) Serum lactate > 2 mmol L-1 despite adequate fluid resuscitation. This subset carries ≈ 40–50 % mortality.

Sepsis Tables

1️⃣ Diagnostic Performance – SIRS vs Biomarker Combinations

Index Test (common cut‑off)	Sensitivity	Specificity	Key Source(s)
SIRS ≥ 2 criteria	0.83 – 0.88	0.29 – 0.49	Large SRs >60k pts
SIRS + Lactate ≥ 2 mmol L‑1	0.74 – 0.77	0.45 – 0.50	ED cohorts, 2023 meta‑analysis
SIRS + Lactate ≥ 3 – 3.5	≈0.67	≈0.71	Prospective ED study
SIRS + CRP ≥ 100 mg L‑1	0.70 – 0.80	≈0.70	CRP meta‑analysis
SIRS + Procalcitonin ≥ 0.5 ng mL‑1	0.77 – 0.80	0.72 – 0.79	2019 & 2023 SRs

Clinical take‑aways: Use SIRS (or NEWS) at triage for sensitivity, then layer procalcitonin ± lactate to rule‑in high‑risk patients; CRP is fallback when PCT isn’t available.

2️⃣ Sepsis Definitions – Classic vs Modern

Framework	Stage	Diagnostic Criteria
Sepsis‑2 (1991/2001)	Sepsis	Suspected infection + ≥2 SIRS signs
	Severe Sepsis	Sepsis + acute organ dysfunction (e.g., lactate >2, Cr ≥2, PLT <100, etc.)
	Septic Shock	Severe sepsis with persistent hypotension despite fluids, requiring vasopressors
Sepsis‑3 (2016)	Sepsis	Suspected infection + ΔSOFA ≥2 (acute organ dysfunction)
	Septic Shock	Sepsis with vasopressor‑dependent MAP <65 and lactate >2 mmol L‑1 post‑resuscitation

⚠️ Severe sepsis was retired in Sepsis‑3; infection + organ dysfunction is now simply called sepsis.

3️⃣ SOFA Score Matrix

Organ System	0 pts	1 pt	2 pts	3 pts	4 pts
Respiratory (PaO2/FiO2)	≥ 400	< 400	< 300	< 200 + support	< 100 + support
Coagulation (Platelets ×10³/µL)	≥ 150	< 150	< 100	< 50	< 20
Liver (Bilirubin mg/dL)	< 1.2	1.2–1.9	2.0–5.9	6.0–11.9	≥ 12.0
Cardiovascular	MAP ≥ 70	MAP < 70	Dopamine ≤ 5 µg/kg/min or any Dobutamine	Dopamine > 5 or Epi/NE ≤ 0.1 µg/kg/min	Dopamine > 15 or Epi/NE > 0.1 µg/kg/min
CNS (GCS)	15	13–14	10–12	6–9	≤ 5
Renal (Creat mg/dL or UO)	< 1.2	1.2–1.9	2.0–3.4	3.5–4.9 or UO < 500 mL/d	≥ 5.0 or UO < 200 mL/d

How to use:

1. Collect worst values for each domain in 24 h.
2. Assign subscores and sum (0–24).
3. ΔSOFA ≥2 with infection = sepsis per Sepsis‑3.

4️⃣ First‑Hour (“Golden Hour”) Sepsis Bundle

Action	Target Timeline	Details
Measure serum lactate	Within 1 hour	Remeasure in 2–4 h if initial >2 mmol L‑1
Obtain blood cultures before antibiotics	Within 1 hour	≥2 sets (aerobic + anaerobic) from separate sites
Administer broad‑spectrum antibiotics	<1 hour (ASAP)	De‑escalate once pathogen & sensitivities known
Give IV crystalloid bolus	Start in 1 hour; complete 30 mL/kg in <3 hours	Use balanced solution when available; reassess fluid responsiveness
Apply vasopressors	Immediately after fluids if MAP <65	First‑line: Norepinephrine; add Vasopressin/EPi as needed
Assess perfusion & organ function	Continuous	qSOFA, urine output, capillary refill, lactate trend

Initiate the bundle as soon as infection + organ dysfunction are suspected; delays >1 h correlate with stepwise mortality increases.

Addendum to below Tables on Aortic Dissection, Chamber Thrombus and Vegetations

Aortic Dissection 

There isn’t a single “fixed” test-characteristic for transthoracic echocardiography (TTE) in aortic dissection—the numbers depend on (1) whether the dissection involves the ascending (Stanford A) or descending (Stanford B) aorta, and (2) how the study defined a “positive” scan (intimal-flap only vs any suggestive sign)

How to interpret these numbers

• High specificity, limited sensitivity. A clearly visualised intimal flap on TTE is highly confirmatory; a negative study—especially when only parasternal/apical windows are obtained—cannot reliably exclude dissection, particularly type B disease.

• Ascending aorta is easier to see. Sensitivity is appreciably better for type A dissections because the proximal aorta and aortic root lie within normal TTE windows. Descending thoracic aorta is often obscured by lung and rib, leading to the much lower sensitivity for type B.

• Technique matters. Adding suprasternal notch views, harmonic imaging, or ultrasound contrast agents, and scanning specifically for any suggestive finding (intimal flap, root dilation, new AR, pericardial effusion) can push sensitivity above 90 %, while preserving high specificity.

• Clinical takeaway. Use TTE as a rapid bedside screen—particularly in haemodynamically unstable patients—knowing that:

• Positive TTE → can expedite surgical/cardiovascular CT confirmation.

• Negative or equivocal TTE → does not rule out dissection; proceed to gated CT angiography or TEE if suspicion remains high.

Vegetations /SBE

Rule of thumb: a positive (clearly mobile) vegetation on TTE is very reliable, but a negative study—especially in prosthetic valves or when image quality is sub-optimal—never rules out infective endocarditis and should be followed by TEE if clinical suspicion is high.

Why the numbers vary

• Vegetation size matters

  • Only ~25 % of vegetations < 5 mm are seen, but ~70 % of those 6–10 mm are detected ccjm.org.

  • Larger, more mobile masses are almost always picked up.

• Image quality & technique

  • Harmonic imaging and contrast agents explain why the recent meta-analysis (61 % sensitivity) out-performs older series from the 1990s (≈45 %).

  • Adding off-axis windows (right parasternal, suprasternal notch) and 3-D sweeps can push sensitivity into the mid-70 % range in experienced labs.

• Valve type

  • Acoustic shadowing from prosthetic material hides small vegetations, so sensitivity drops to ~30–50 %.

  • Conversely, specificity stays high because artefacts that mimic vegetations are well recognised.

Practical take-aways for reporting & patient care

1. Use TTE first for haemodynamically stable patients—it is fast, non-invasive, and will confirm IE in roughly two-thirds of native-valve cases.

2. Escalate to TEE (or gated cardiac CT/PET-CT for prostheses) when:

   • TTE is negative/equivocal but Duke or ESC/ACC clinical likelihood remains high.

   • The patient has a prosthetic valve, intracardiac device leads, prior surgery, or poor acoustic windows.

3. Repeat imaging 3–7 days later if suspicion persists; early vegetations may enlarge and become visible.

4. Document limitations in every negative TTE report: comment on image quality and indicate that small or prosthetic-masked vegetations cannot be excluded.

Bottom line: expect TTE to spot about two-thirds of native-valve vegetations and only one-half (or fewer) of prosthetic-valve vegetations, while maintaining >90 % specificity—hence the need for reflex TEE when the diagnosis still matters.

Any Chamber Thrombus

How to use these numbers in practice

• High specificity across the board – when you see a discrete, echo-dense mass with independent mobility at the expected location, it is very likely a true thrombus and should prompt treatment or confirmatory imaging rather than further scepticism.

• Sensitivity is chamber-dependent:

  • LV thrombus is easiest because the apex is usually in the near field; nevertheless, up to 40 % are still missed without contrast or apical-wall-motion scoring.

  • LA/LAA thrombus is routinely missed on TTE; a negative study never rules it out when the appendage is clinically relevant (e.g., before cardioversion). Proceed to TEE or CT.

  • Right-sided thrombi are rarer and often located in recesses or on hardware. Modified apical/sub-costal views and a focused search improve yield but many series still report only half of RV or 1 in 3 RA thrombi being seen on TTE.

• Contrast & advanced techniques help: LV opacifying agents or harmonic imaging increase sensitivity by ~15 %. There is emerging experience with intracavity contrast for atrial clots, but it is not yet routine.

• Report responsibly: For atrial or right-heart chambers, avoid a blanket “no thrombus” statement unless image quality genuinely excludes it; instead describe the acoustic windows and say “No thrombus seen; small or appendage thrombus cannot be excluded.”

Bottom line:
TTE is a rule-in tool for intracardiac thrombus – a positive finding is trustworthy – but its rule-out value varies: good for LV, modest for LA/LAA, and poor for RA/RV. When missing a clot has therapeutic consequences, reflex to TEE, cardiac CT or CMR.

Sensitivity and Specificity of Various ECHO Findings

Transthoracic Echo (TTE) for Aortic Dissection

Population / Technique	Sensitivity	Specificity
Any dissection (mixed Stanford A + B)	≈ 62 %	≈ 88 %
Ascending (Stanford A)	≈ 85 %	≈ 85 %
Descending (Stanford B)	≈ 46 %	≈ 87 %
Contrast-enhanced TTE (proximal)	up to 93 %	up to 97 %

Practical take-away: TTE is specific but not fully sensitive. A clear intimal flap is confirmatory; a negative TTE—especially for type B—must be followed with gated CT or TEE if suspicion remains high.

TTE for Detecting Vegetations (Infective Endocarditis)

Valve / Setting	Sensitivity	Specificity
Native valves	≈ 60–70 %	≈ 90–95 %
Prosthetic valves	≈ 30–55 %	≈ 85–90 %

Key points:

• TTE reliably rules-in IE when a mobile mass is seen, but a negative scan—especially with prosthetic valves—does not exclude the disease.
• Vegetation size and image quality dominate performance; consider harmonic imaging or early TEE when clinical suspicion is high.

TTE Sensitivity / Specificity for Intracardiac Thrombus

Chamber	Sensitivity	Specificity	Notes
Left Ventricle (LV)	≈ 55–60 %	≈ 95–99 %	Contrast boosts sensitivity to ~64 %
Left Atrium / LAA	≈ 40–60 %	≈ 90–94 %	Poor appendage visualisation; use TEE
Right Atrium (RA)	≈ 30 %	≈ 100 %	Few false-positives but many misses
Right Ventricle (RV)	≈ 40–50 %	> 90 %	Non-standard views improve yield

Clinical pearls: LV thrombus is the most detectable on TTE; atrial and right-sided clots are frequently missed. A positive TTE finding across chambers is highly specific and should trigger therapy or confirmatory imaging; a negative study rarely rules out LA/LAA or right-heart thrombus when management decisions hinge on exclusion.

Anti-Emetic Tool Box

ICU Anti‑Emetic Toolbox

1. Dopamine‑2 Antagonists / Pro‑kinetics

Agent	Typical ICU Dose	Pearls & ICU Cautions
Metoclopramide	5–10 mg IV q6 h	Anti‑emetic & pro‑kinetic; risk of akathisia/dystonia; ↓dose if CrCl < 40 mL/min
Haloperidol	1–2 mg IV q4–6 h PRN	Useful when agitation co‑exists; monitor QTc
Droperidol	0.625–1.25 mg IV ×1 (may repeat ×1)	Rapid onset; torsades risk—use with continuous ECG
Prochlorperazine	5–10 mg IV q6 h	Potent; EPS common—consider diphenhydramine cover

2. 5‑HT₃ (Serotonin) Receptor Antagonists

Agent	Typical ICU Dose	Pearls & ICU Cautions
Ondansetron	4 mg IV q6 h PRN (up to 8 mg)	Minimal sedation; mild QT prolongation; limit dose in severe hepatic impairment
Granisetron	1 mg IV q12 h	Longer half‑life than ondansetron; option for refractory cases

3. Antihistamine / Anticholinergic

Agent	Typical ICU Dose	Pearls & ICU Cautions
Diphenhydramine	25–50 mg IV q6 h PRN	Helpful for vestibular or medication‑induced NV; sedation & anticholinergic delirium in elderly
Promethazine	12.5–25 mg IV q6 h (slow, diluted)	Potent; vesicant—use large IV line; hypotension and sedation common
Scopolamine patch	1 patch q72 h	Great for vestibular & opioid taper NV; mydriasis—avoid in narrow‑angle glaucoma

Practical ICU Tips

• Start with the likely mechanism: gastroparesis → metoclopramide; opioid withdrawal → haloperidol; vestibular → diphenhydramine.
• Watch the ECG: Many agents prolong QT; obtain baseline & 2–4 h post‑dose ECG when stacking risks.
• Use combination therapy (e.g., 5‑HT₃ + dexamethasone + haloperidol) for refractory cases.
• Adjust for organ dysfunction: reduce metoclopramide in renal failure; limit ondansetron in severe hepatic disease.
• Route matters: IV or transdermal if bowel not functioning; consider NG/OG formulations for long‑term ventilation.
• Re‑evaluate daily: Persistent NV may signal underlying pathology—treat the cause, not just the symptom.

4. Neurokinin‑1 (NK₁) Receptor Antagonists

Agent	Typical ICU Dose	Pearls & ICU Cautions
Fosaprepitant	150 mg IV ×1 (24 h coverage)	Synergistic with 5‑HT3 blockers & steroids; CYP interactions (warfarin, tacrolimus)

5. Corticosteroid

Agent	Typical ICU Dose	Pearls & ICU Cautions
Dexamethasone	4–8 mg IV ×1–2 day	Adjunct for peri‑op, ↑ICP, bowel‑wall edema; onset 2–4 h; monitor glucose/WBC

6. Atypical Antipsychotic

Agent	Typical ICU Dose	Pearls & ICU Cautions
Olanzapine	2.5–5 mg PO/ODT/NG q12–24 h	Refractory chemo‑induced & multifactorial NV; sedation & hypotension; monitor QT

7. Adjunct / Special‑Situation Agents

Situation	Useful Agent(s)	Rationale
Severe gastroparesis / ileus	Erythromycin 250 mg IV q6 h	Short‑term pro‑kinetic; tachyphylaxis in 48–72 h; QT risk
Migraine‑associated NV	IV prochlorperazine ± diphenhydramine	Targets dopaminergic pathway; add IV fluids & magnesium
Cannabinoid hyperemesis	Haloperidol or droperidol	Superior symptom control vs ondansetron in studies
Anxiety‑triggered NV	Lorazepam 0.5–1 mg IV q4 h PRN	Combine with primary anti‑emetic; avoid oversedation

Quick First‑Line Cheat Sheet

Scenario	Go‑to First Dose
Undifferentiated ICU NV	Ondansetron 4 mg IV
Gastroparesis / tube‑feed intolerance	Metoclopramide 10 mg IV
Post‑op NV resistant to ondansetron	Droperidol 0.625 mg IV
Opioid‑exposed, agitated	Haloperidol 1 mg IV
Refractory / high emetogenic chemo	Fosaprepitant 150 mg IV + Ondansetron 8 mg IV + Dexamethasone 8 mg IV

Cannabinoids as Anti‑Emetics

Cannabinoid agonists activate CB₁ receptors in the brainstem vomiting center and enteric plexus, dampening both nausea perception and the motor drive to vomit. They pre‑date modern 5‑HT₃/NK₁ regimens and remain a fallback when standard agents fail—particularly in highly emetogenic chemotherapy or stubborn, multifactorial nausea.

FDA‑Approved Products (United States)

Product (brand)	Formulation / Schedule	Usual Anti‑Emetic Dose*	Approved Indication†	Practical ICU / Bedside Notes
Dronabinol (Marinol®)	2.5 / 5 / 10 mg oral capsules Schedule III	5 mg/m2 PO 1–3 h before chemo; then q2‑4 h × 4–6 doses/day (max 15 mg/m2/day)	CINV after failure of conventional anti‑emetics; AIDS‑related anorexia	Swallow intact; onset 30–60 min—better for prophylaxis. Capsule can be opened for NG administration if needed.
Dronabinol (Syndros®)	5 mg/mL oral solution Schedule II	Same mg/m2 schedule as capsules (administer with calibrated oral syringe)	Same as Marinol®	Faster absorption; alcohol‑containing vehicle—caution with hepatic impairment or disulfiram use.
Nabilone (Cesamet®)	1 mg capsules Schedule II	1–2 mg PO BID; start 1–3 h before chemo, continue BID ≤ 48 h after last dose	CINV refractory to standard therapy	Longer half‑life than dronabinol; no renal adjustment; chiefly hepatic metabolism.

*Adult dosing—titrate to lowest effective dose to limit CNS effects.
†All require prior failure of first‑line anti‑emetics per FDA labeling.

Preparations Not FDA‑Approved for NV

• Nabiximols (Sativex®): 1:1 THC:CBD oromucosal spray approved in Canada/UK for MS spasticity; small trials suggest CINV benefit but not FDA‑approved.
• Whole‑plant medical cannabis: Inhaled or edible forms legal in some U.S. states; THC/CBD ratio and bioavailability vary—not advised in critical‑care settings.

Practical ICU Considerations

1. Reserve for refractory cases – Current NCCN/ASCO algorithms place cannabinoids after failure of 5‑HT₃ + dexamethasone ± NK₁ ± olanzapine.
2. Route limitations – All FDA‑approved products are oral; require functioning GI tract or enteral tube.
3. Adverse effects – Euphoria/dysphoria, sedation, tachycardia, orthostatic hypotension, potential delirium; start low, reassess frequently.
4. Drug interactions – CYP2C9/3A4 substrates; monitor when co‑administered with azoles, macrolides, ritonavir, warfarin, tacrolimus.
5. Legal & storage considerations – Controlled‑substance handling: Schedule II (Cesamet, Syndros) vs Schedule III (Marinol); observe unit storage policies.

Bottom line: Synthetic cannabinoid agents offer a legally sanctioned, evidence‑based fallback for chemotherapy‑related nausea unresponsive to modern first‑line regimens. In the ICU they remain third‑line tools because of psychoactive side‑effects and oral‑only administration, but can salvage otherwise intractable nausea when used judiciously.

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.

Shivering in TTM-Treatment

Tier (progression)	Intervention(s) & Typical Dosing	Key Points / When to Move On
0 – Preventive non-sedating	• Skin counter-warming: forced-air blanket ≈ 43 °C • Acetaminophen 650–1000 mg IV/PO q4-6 h • Buspirone 30 mg PO/NG q8 h • Magnesium SO4 2 g IV load, then 0.5–1 g h-1 (goal Mg 3–4 mg/dL)	Start before cooling. Escalate if BSAS ≥ 2 despite these.
1 – Mild sedation single agent	Choose one: • Dexmedetomidine 0.2–1.5 µg kg-1 h-1 IV or • Opioid (e.g., Fentanyl 25–100 µg h-1 or Meperidine 25–50 mg IV q4-6 h / 12.5–35 mg h-1 infusion)	Re-score BSAS after titration; add second class if BSAS ≥ 2.
2 – Moderate sedation dual therapy	Dexmedetomidine plus opioid (Tier 1 doses) & continue Tier 0 measures.	Synergistic effect. Move to Tier 3 if shivering persists or deep sedation already needed.
3 – Deep sedation	• Propofol 50–75 µg kg-1 min-1 (up to 200 µg kg-1 min-1 if tolerated) • Continue earlier-tier agents as needed	Aim BSAS 0-1; watch for hypotension, hyper-triglyceridemia, PRIS.
4 – Neuromuscular blockade	Preferred Cisatracurium: 0.15 mg kg-1 bolus, then 1–3 µg kg-1 min-1 Alternate Vecuronium: 0.1 mg kg-1 bolus, then 0.8–1.2 µg kg-1 min-1	Use after adequate analgesia/sedation; reassess daily, monitor TOF 1–2/4.

Practical Tips & Adjuncts

• Sedation foundation: Most postarrest patients are intubated; pair this algorithm with baseline analgesia (e.g., fentanyl) and light sedation even at Tier 0.
• Adjunct/rescue agents (if limited by side-effects): low-dose ketamine 0.1–0.5 mg kg^-1 h^-1, clonidine 0.1–0.2 mg PO/NG, ondansetron 4 mg IV, or dantrolene 2.5 mg kg^-1 IV.
• Monitoring: Check BSAS hourly, core temperature continuously, and serum magnesium & triglycerides daily.
• Weaning sequence: During re-warming, stop NMB first, then propofol, then dexmedetomidine/opioids; keep Tier 0 measures until normothermia has been shiver-free for ≥ 4 h.

What Is the BSAS?

The Bedside Shivering Assessment Scale (BSAS) is a quick 4-point scale used at the bedside to grade the intensity of shivering during targeted-temperature management. The goal during TTM is a BSAS of 0–1.

Score	Shivering Description	Clinical Notes
0 (None)	No shivering detected on visual inspection or palpation of masseter, neck, or chest wall.	Target value during cooling; no metabolic penalty.
1 (Mild)	Shivering localized to the neck and/or thorax; may appear only as ECG artifact.	Begin Tier 0–1 measures if persistent.
2 (Moderate)	Intermittent shivering involving upper extremities ± thorax.	Escalate to dual therapy (Tier 2) if not already in use.
3 (Severe)	Generalized or sustained shivering involving the entire body.	Requires deep sedation or neuromuscular blockade (Tier 3–4).

Suggested assessment frequency: every 15–30 min during induction, hourly during maintenance, and every 30 min during re-warming.