🫁 GINA 2026
Updated May 2026
Global Strategy for Asthma Management and Prevention
Global Initiative for Asthma (GINA) — Science Committee
Source: Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2026 (Updated May 2026).
© 2026 Global Initiative for Asthma.
Full report (free access): ginasthma.org/reports · Suggested citation: Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2026. Available from: www.ginasthma.org
Full report (free access): ginasthma.org/reports · Suggested citation: Global Initiative for Asthma. Global Strategy for Asthma Management and Prevention, 2026. Available from: www.ginasthma.org
What's New in GINA 2026
🔄 Acute Asthma Flowcharts New
Four new standardised flowcharts for acute exacerbation management — primary care and ED, for adults/adolescents and children ≤5 years. Criteria for mild / moderate / severe / life-threatening presentations with step-by-step treatment and discharge planning.
💉 Anaphylaxis + Asthma New
If features of anaphylaxis co-exist: give epinephrine (adrenaline) first, then bronchodilators — recommendation added to all acute flowcharts.
📊 New Assessment Tools New
CAAT (Chronic Airways Assessment Test) — 8-item validated tool for adults, covering sputum & energy.
Peds-AIRQ — composite control score for children 5–11 years.
PRAM — strongly recommended for severity scoring in children <18 years with acute exacerbation.
Peds-AIRQ — composite control score for children 5–11 years.
PRAM — strongly recommended for severity scoring in children <18 years with acute exacerbation.
🩺 OCS Stewardship New
Priority to reduce oral corticosteroid (OCS) use. Optimise inhaled therapy; biologic therapy where indicated; appropriate dose/duration for OCS courses; non-pharmacological techniques.
🌡️ Vaccines Updated
Evidence updated for influenza, RSV, and COVID-19 vaccines — all recommended for asthma patients. Maternal immunisation protects against asthma exacerbations in infants.
💊 Track 1 Simplified
Dose instructions for ICS-formoterol AIR/MART simplified. "Maximum dose" language replaced with a prompt to seek medical care if >12 inhalations (adults) needed in 24 h.
Definition & Diagnosis
Asthma is a heterogeneous disease, usually characterised by chronic airway inflammation. Defined by a history of respiratory symptoms (wheeze, shortness of breath, chest tightness, cough) that vary over time and intensity, together with variable expiratory airflow limitation.
Symptom Pattern
Symptoms vary over time · worse at night/on waking · triggered by exercise, laughter, allergens, cold air · worsen with viral infections · worsen after stopping exercise (very distinctive)
Confirmed Variable Airflow
BD reversibility (spirometry): FEV₁ increase ≥12% and ≥200 mL from baseline after 200–400 mcg salbutamol.
PEF variability: diurnal variation >10% (adults) averaged over 2 weeks.
PEF variability: diurnal variation >10% (adults) averaged over 2 weeks.
Asthma Control Assessment
Control is assessed in two domains: (1) Symptom control over the past 4 weeks, and (2) Risk of adverse future outcomes.
| Domain | Well Controlled | Partly Controlled | Uncontrolled |
|---|---|---|---|
| Daytime symptoms >2×/week | None of 4 | 1–2 of 4 | 3–4 of 4 |
| Night waking due to asthma | Ask in past 4 weeks; each "Yes" counts as 1 item toward the 4-question total above | ||
| SABA reliever use >2×/week | (Exclude use before exercise) | ||
| Any activity limitation | Work, school, home activities | ||
| Risk factors for poor outcomes | Uncontrolled symptoms · ≥1 exacerbation in past year · over-use of SABA (≥3 canisters/year) · low FEV₁ · smoking · high FeNO or blood eosinophils · poor adherence/inhaler technique · chronic sinusitis | ||
Treatment Tracks — Adults & Adolescents
GINA Track 1 (Preferred): ICS-formoterol as anti-inflammatory reliever (AIR) at every step. Reduces severe exacerbations, systemic corticosteroid exposure, and need for urgent healthcare compared with SABA-based regimens. Single medication, single dose, single inhaler across Steps 1–4.
Track 2 (Alternative): ICS-SABA or SABA reliever — use if Track 1 unavailable or asthma is stable on current regimen.
Track 2 (Alternative): ICS-SABA or SABA reliever — use if Track 1 unavailable or asthma is stable on current regimen.
| Step | Track 1 — Preferred (ICS-formoterol reliever) | Track 2 — Alternative (SABA/ICS-SABA reliever) |
|---|---|---|
| Step 1–2 Mild / infrequent |
✦ AIR only As-needed low-dose ICS-formoterol (budesonide/formoterol or beclometasone/formoterol). No daily maintenance. |
As-needed low-dose ICS+SABA (combination or separate inhalers) or as-needed SABA alone (Step 1 only — not recommended by GINA). |
| Step 3 Moderate persistent |
✦ MART Low-dose ICS-formoterol daily (maintenance) + as-needed (reliever) — same inhaler. |
Low-dose ICS-LABA maintenance + as-needed SABA. |
| Step 4 Moderate–severe |
✦ MART Medium-dose ICS-formoterol daily + as-needed (same inhaler). |
Medium-dose ICS-LABA + as-needed SABA. Consider adding LAMA. |
| Step 5 Severe / refractory |
Refer for expert phenotyping. Add-on therapy: LAMA (triple inhaler) · Biologic therapy (based on Type 2 biomarkers) · Bronchial thermoplasty (selected patients) · OCS only as last resort. | |
ICS-formoterol dosing (adults): Budesonide/formoterol 160/4.5 mcg DPI or beclometasone/formoterol 100/6 mcg DPI.
Step 1–2 AIR: 1 inhalation as needed. Step 3 MART: 1 inhalation twice daily + 1 as needed. Step 4 MART: 2 inhalations twice daily + 1 as needed.
Seek medical care if >12 inhalations needed in 24 h.
ICS-formoterol is the only ICS-LABA approved for MART.
Children 6–11 Years
- Step 1: As-needed low-dose ICS-formoterol or as-needed low-dose ICS+SABA (combination or separate).
- Step 2: Daily low-dose ICS + as-needed ICS-formoterol or SABA. LTRA is alternative but less effective and carries neuropsychiatric risk.
- Step 3: Low-dose ICS-formoterol MART (1 inhalation once daily + 1 as needed).
- Step 4: Medium-dose ICS-LABA + as-needed SABA or MART with increased dose. Refer for expert advice.
- SABA alone is NOT recommended at any step in any age group.
Step 5 — Biologic Therapy (Severe Type 2 Asthma)
Anti-IgE: Omalizumab
Blocks free IgE → prevents mast cell / basophil activation
Allergic asthma. Elevated total IgE and sensitisation to perennial allergen. SC every 2–4 weeks.
Anti-IL5: Mepolizumab, Benralizumab
Targets IL-5 (or its receptor) → reduces eosinophil production & survival
Eosinophilic asthma (high blood eosinophils). Mepolizumab SC monthly; benralizumab SC every 4 weeks × 3, then every 8 weeks.
Anti-IL4Rα: Dupilumab
Blocks IL-4 & IL-13 signalling → broad Type 2 suppression
Type 2 asthma with raised eosinophils or elevated FeNO. Also approved for atopic dermatitis, CRS/NP. SC every 2 weeks.
Anti-TSLP: Tezepelumab
Blocks TSLP (epithelial alarmin) → upstream blockade of Type 2 & non-Type 2 inflammation
Broadest eligibility — benefits across eosinophil subgroups. SC every 4 weeks.
Exacerbation Management — Key 2026 Updates
- Spirometry (or PEF) recommended for all patients on presentation and before discharge — not for preschool children or life-threatening presentations.
- Anaphylaxis co-existing: Epinephrine (adrenaline) first, then bronchodilators.
- Discharge = a teachable moment: Every exacerbation needing urgent care or OCS is a "red flag" to review and step up maintenance treatment.
- Lung function on presentation allows confirmation of diagnosis via pre/post-bronchodilator testing — document in the medical record.
- PRAM score strongly recommended for severity grading in all children <18 years presenting acutely.
❤️ ACC/AHA 2026
Published 2026
Guideline on the Management of Dyslipidemia
ACC/AHA Joint Committee · Co-endorsed by AACVPR, ADA, AGS, NLA, PCNA and 6 other societies
Source: 2026 ACC/AHA/AACVPR/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA Guideline on the Management of Dyslipidemia.
A Report of the American College of Cardiology/American Heart Association Joint Committee on Clinical Practice Guidelines.
Full guideline: acc.org/guidelines · Journal of the American College of Cardiology / Circulation
Full guideline: acc.org/guidelines · Journal of the American College of Cardiology / Circulation
Top Take-Home Messages — 2026
🎯 LDL-C Goals Are Back New
Both absolute LDL-C goals and % reduction targets are recommended — a departure from the 2018 guideline which focused only on % reduction.
📐 Use PREVENT Equations New
Replace the Pooled Cohort Equations (PCE) with the newer AHA PREVENT™ equations for 10-year and 30-year ASCVD risk estimation in adults 30–79 years. Apply the "CPR" model: Calculate → Personalise → (Re)classify.
⏰ Treat Earlier
Start lifestyle counselling in childhood; consider pharmacotherapy in youth with familial hypercholesterolaemia (FH) and in young adults with LDL-C ≥160 mg/dL or strong family history of premature ASCVD.
📊 ApoB & Lp(a) Routinely
Lp(a) measured at least once in all adults. ApoB useful when LDL-C/non-HDL-C goals are met but residual risk persists (especially with elevated TG, diabetes, or low achieved LDL-C <70).
🔬 CAC Scoring
Coronary artery calcium (CAC) scoring in men ≥40 years and women ≥45 years improves risk reclassification and guides LDL-C goals — consider before starting statin in borderline-risk individuals.
🚫 No Supplements
Dietary supplements (including fish oil, red yeast rice, plant sterols) are not recommended for LDL-C or TG lowering based on limited, inconsistent data. (Class 3: No Benefit)
Screening & Measurement
- Adults: Lipid profile starting at age 19, at least every 5 years; more frequent if additional ASCVD risk factors are present.
- Children: Screen at 9–11 years with lipid profile. If family history of premature ASCVD, severe hypercholesterolaemia, or FH: cascade screening from ≥2 years of age.
- Preferred LDL-C estimation: Martin/Hopkins or Sampson/NIH equation (preferred over Friedewald — especially when TG are elevated or LDL-C is very low).
- Non-HDL-C reporting: Mandatory in all lipid profiles for ASCVD risk assessment and LLT guidance.
- Lp(a): Measure at least once in all adults. ≥125 nmol/L (≥50 mg/dL) is a risk-enhancing factor (~1.4× ASCVD risk); ≥250 nmol/L (~2× or higher risk).
LDL-C & Non-HDL-C Treatment Goals by Risk Category
| Risk Category | LDL-C Goal | Non-HDL-C Goal | First-Line Therapy |
|---|---|---|---|
| Very High Risk ASCVD Recurrent events, multi-vessel disease, or ASCVD + DM/CKD/HeFH |
<55 mg/dL (1.4) | <85 mg/dL (2.2) | COR 1 High-intensity statin → add ezetimibe → add PCSK9 mAb/bempedoic acid |
| Clinical ASCVD (not very high risk) First ASCVD event, stable |
<70 mg/dL (1.8) | <100 mg/dL (2.6) | COR 1 High-intensity statin → add ezetimibe / PCSK9 mAb / bempedoic acid if not at goal |
| Primary Prevention — High Risk 10-year ASCVD risk ≥10%, or DM/CKD/HIV (age 40–75) |
≥50% LDL-C reduction | <100 mg/dL (2.6) | COR 1 High-intensity statin |
| Primary Prevention — Intermediate 10-year ASCVD risk 5% to <10% |
<100 mg/dL (2.6) | <130 mg/dL (3.4) | COR 2a Moderate-intensity statin (≥30–49% LDL-C reduction) |
| Primary Prevention — Borderline New 10-year ASCVD risk 3% to <5% |
<100 mg/dL (2.6) | <130 mg/dL (3.4) | COR 2a Moderate-intensity statin after clinician–patient discussion |
| Primary Prevention — Low Risk + LDL-C 160–189 mg/dL New 10-year ASCVD risk <3% but LDL-C ≥160 or 30-year risk ≥10% |
≥30% LDL-C reduction | — | COR 2a Moderate-intensity statin — reduce cumulative atherogenic lipoprotein exposure |
| Severe Hypercholesterolaemia LDL-C ≥190 mg/dL (4.9), no ASCVD |
<100 mg/dL (2.6) | <130 mg/dL (3.4) | COR 1 Maximally tolerated statin + ezetimibe + PCSK9 mAb and/or bempedoic acid |
| Severe Hypercholesterolaemia + ASCVD LDL-C ≥190 mg/dL + clinical ASCVD |
<55 mg/dL (1.4) | <85 mg/dL (2.2) | COR 1 Statin + ezetimibe + PCSK9 mAb and/or bempedoic acid |
| Diabetes (age 40–75, no ASCVD) | <100 mg/dL (2.6) | <130 mg/dL (3.4) | COR 1A Moderate-intensity statin; high-intensity if multiple risk factors (goal <70) |
| CKD Stage 3+ (age 40–75) | ≥50% reduction | — | COR 1 Moderate-intensity statin ± ezetimibe; high-intensity if ASCVD co-exists |
| CAC ≥1000 AU New | <55 mg/dL (1.4) | <85 mg/dL (2.2) | COR 1 LDL-C lowering — statin first line; escalate to ezetimibe/PCSK9i if needed |
Lipid-Lowering Drug Classes
Statins (HMG-CoA reductase inhibitors)
Inhibit hepatic cholesterol synthesis → upregulate LDL receptors
First-line for nearly all patients. LDL-C reduction: 18–55% depending on agent and dose.
High-intensity: Atorvastatin 40–80 mg, Rosuvastatin 20–40 mg (≥50% LDL-C reduction).
Moderate-intensity: Atorvastatin 10–20 mg, Rosuvastatin 5–10 mg, Simvastatin 20–40 mg (30–49%).
High-intensity: Atorvastatin 40–80 mg, Rosuvastatin 20–40 mg (≥50% LDL-C reduction).
Moderate-intensity: Atorvastatin 10–20 mg, Rosuvastatin 5–10 mg, Simvastatin 20–40 mg (30–49%).
Ezetimibe
Inhibits NPC1L1 → reduces intestinal cholesterol absorption
10 mg once daily. Reduces LDL-C by ~18–25% added to statin. Well tolerated. First add-on if statin alone insufficient. Safe in CKD. Monitor LFTs when added to statin.
PCSK9 mAbs — Evolocumab, Alirocumab
Monoclonal antibodies block PCSK9 → more LDL receptors on hepatocytes
SC every 2 weeks or monthly. LDL-C reduction 50–65%. Proven cardiovascular outcomes (FOURIER, ODYSSEY). Recommended for very high risk, severe hypercholesterolaemia, and elevated Lp(a) not at goal.
Bempedoic Acid Expanded role
ATP-citrate lyase inhibitor → reduces hepatic cholesterol synthesis upstream of HMG-CoA
180 mg once daily oral. LDL-C reduction ~18–25%. Not activated in muscle → fewer muscle symptoms. Proven CV outcome benefit (CLEAR trial). Useful in statin intolerance. Watch: elevated uric acid, gout.
Inclisiran New recommendations
siRNA — silences PCSK9 mRNA in hepatocytes → durable LDL-C reduction
SC at day 0, 3 months, then every 6 months. LDL-C reduction ~50%. CV outcomes trials pending — currently indicated only to lower LDL-C. Reasonable for severe hypercholesterolaemia ≥100 mg/dL despite statin ± ezetimibe, or for statin-intolerant patients preferring less frequent dosing.
Icosapent Ethyl (IPE)
Highly purified EPA omega-3 → reduces TG and pleiotropic effects
4 g daily. For adults ≥50 years with ASCVD or DM + ≥1 ASCVD risk factor, TG 150–499 mg/dL, LDL-C <100 mg/dL on maximal statin. Watch for atrial fibrillation. (REDUCE-IT trial)
Olezarsen New
ASO (antisense oligonucleotide) targeting ApoC-III mRNA → reduces TG
SC monthly. For familial chylomicronaemia syndrome (FCS) with TG ≥1000 mg/dL — COR 1 to reduce risk of pancreatitis.
Evinacumab (HoFH)
Anti-ANGPTL3 mAb → reduces TG and LDL-C via LDL-receptor-independent pathway
For homozygous FH (HoFH) on maximal statin + ezetimibe + PCSK9i with LDL-C ≥100 mg/dL. IV every 4 weeks. Requires specialist lipid clinic.
Special Situations
Elevated Lp(a)
Measure once in all adults.
≥125 nmol/L or ≥50 mg/dL: Optimise modifiable CV risk factors — COR 1.
ASCVD + elevated Lp(a) not at LDL/non-HDL goal on maximal statin: Add PCSK9 mAb — COR 1.
Cascade screen first-degree relatives.
≥125 nmol/L or ≥50 mg/dL: Optimise modifiable CV risk factors — COR 1.
ASCVD + elevated Lp(a) not at LDL/non-HDL goal on maximal statin: Add PCSK9 mAb — COR 1.
Cascade screen first-degree relatives.
Statin Intolerance (Muscle Symptoms)
Exclude secondary causes (hypothyroidism, vitamin D deficiency, DDIs).
Counsel: ASCVD risk increases with statin discontinuation.
Options: reduce statin dose + add bempedoic acid and/or ezetimibe.
If ASCVD + unable to achieve goal: add PCSK9 mAb or inclisiran — COR 1.
Counsel: ASCVD risk increases with statin discontinuation.
Options: reduce statin dose + add bempedoic acid and/or ezetimibe.
If ASCVD + unable to achieve goal: add PCSK9 mAb or inclisiran — COR 1.
Hypertriglyceridaemia
TG 150–499 mg/dL: Lifestyle first (low sugar, low refined carbs, reduce alcohol, exercise, weight loss 5–10%).
TG 500–999 mg/dL: Above + consider fenofibrate (not gemfibrozil with statin).
TG ≥1000 mg/dL: Very low fat diet; consider olezarsen (FCS) or fibrate + specialist referral.
TG 500–999 mg/dL: Above + consider fenofibrate (not gemfibrozil with statin).
TG ≥1000 mg/dL: Very low fat diet; consider olezarsen (FCS) or fibrate + specialist referral.
Pregnancy & Lactation
Statins: Stop 1–2 months before planned pregnancy (FDA removed absolute contraindication but most stop).
Bile acid sequestrants: Safe (no systemic absorption). Monitor fat-soluble vitamins.
Ezetimibe, PCSK9i, inclisiran, bempedoic acid: Avoid — insufficient safety data.
Bile acid sequestrants: Safe (no systemic absorption). Monitor fat-soluble vitamins.
Ezetimibe, PCSK9i, inclisiran, bempedoic acid: Avoid — insufficient safety data.
Older Adults (>75 years)
Benefit-risk discussion considering priorities, frailty, polypharmacy, life expectancy — not age alone.
Life expectancy ≥2.5 years: Moderate-intensity statin reasonable — COR 2b.
Life expectancy <1 year: May discontinue LLT to avoid unnecessary burden — COR 2b.
Life expectancy ≥2.5 years: Moderate-intensity statin reasonable — COR 2b.
Life expectancy <1 year: May discontinue LLT to avoid unnecessary burden — COR 2b.
Children & Adolescents
Lifestyle management first for all — COR 1.
Age ≥8 years with LDL-C ≥160 mg/dL consistent with FH, unresponsive after 3–6 months lifestyle: Initiate statin — COR 1.
Genetic panel testing for FH useful (COR 2a) to guide cascade testing and treatment.
Age ≥8 years with LDL-C ≥160 mg/dL consistent with FH, unresponsive after 3–6 months lifestyle: Initiate statin — COR 1.
Genetic panel testing for FH useful (COR 2a) to guide cascade testing and treatment.
Safety Pearls
- Diabetes risk and statins: Continue statin therapy if new-onset diabetes develops; the cardiovascular benefit far outweighs risk — COR 1A.
- Liver disease (including MASLD/NAFLD): Statin therapy is reasonable and safe in stable chronic liver disease — COR 2a.
- CoQ10 supplementation: Not recommended to prevent statin muscle symptoms — Class 3 No Benefit.
- Routine CK monitoring: Not indicated in asymptomatic statin users — Class 3 No Benefit.
- Routine LFT monitoring: Not required without symptoms of hepatotoxicity — Class 3 No Benefit.
- HIV (age 40–75 on stable ART): Statin therapy recommended to reduce first ASCVD event — COR 1.
- Cancer survivors (life expectancy ≥2 years): Treat lipids as in those without cancer history — COR 1.
- Statin + amiodarone: Limit lovastatin to 40 mg/day, simvastatin to 20 mg/day.
⚠️ Educational use only. This page presents a distilled summary for study purposes. It does not replace the full guideline documents, local formulary decisions, or clinical judgement. Always consult the source guidelines and current local protocols before prescribing. Content is accurate as of May 2026.
🧠 ICS 2025
Published 2025 · JICS Vol. 26(2)
Guidelines for the Management of Status Epilepticus in Critical Care
Mullhi D et al. · The Intensive Care Society · Multi-specialty consensus: acute medicine, neurology, ICU & emergency medicine
Source: Mullhi D et al. Guidelines for the Management of Status Epilepticus in Critical Care.
Journal of the Intensive Care Society, 2025; 26(2): 249–262. © The Intensive Care Society 2025.
DOI: 10.1177/17511437251321338 · SAGE Publications. Scope: adults ≥16 yr; excludes obstetric population.
DOI: 10.1177/17511437251321338 · SAGE Publications. Scope: adults ≥16 yr; excludes obstetric population.
🔖 Key Definitions (ILAE Classification)
Status Epilepticus (SE)
≥ 5 minutes of continuous seizures, or repetitive seizures with no intervening recovery of consciousness. (Previously >30 min — revised to stress early treatment, as prognosis worsens with duration.)
Convulsive SE (CSE)
Generalised rhythmic limb jerking + impaired consciousness fulfilling SE criteria. Medical emergency — immediate treatment required.
Non-Convulsive SE (NCSE)
SE without prominent motor component. Diagnosis depends on EEG findings. NCSE with impaired consciousness → high mortality → treat as CSE. Can follow CSE and cause unexplained coma.
Refractory SE (RSE)
SE not responding to 1 benzodiazepine + 1 non-BZD anti-seizure medication (ASM). Requires ICU admission and IV anaesthesia to suppress seizures.
Super-Refractory SE (SRSE)
SE continuing or recurring despite adequate continuous IV anaesthetic infusion for >24 hours. Often associated with autoimmune encephalitis. Refer to tertiary neurocritical care.
NORSE / FIRES
NORSE: New-onset RSE in a patient without prior epilepsy or neurological disorder, with no clear structural, metabolic or toxic cause. FIRES: Febrile infection-related epilepsy syndrome (NORSE subcategory).
⚡ 5-Stage Treatment Algorithm
| Stage | Time | Action | Key Drugs & Doses |
|---|---|---|---|
| Stage 1 | 0 min | Stabilise patient (Ward / ED) | Airway · Breathing · Circulation · Glucose — correct hypoglycaemia immediately |
| Stage 2 | 0–15 min | Rescue benzodiazepine | Lorazepam 4 mg IV (0.1 mg/kg, max 4 mg) or Buccal midazolam 10 mg. May repeat once after 5–10 min if seizures continue. |
| Stage 3 | 15–30 min | Urgent CCU senior review. 2nd-line non-sedating ASM — no agent proven superior; choice is patient-dependent. | Levetiracetam 60 mg/kg IV (max 4500 mg) over 10 min or Sodium valproate 40 mg/kg IV (max 3000 mg) over 10 min or Phenytoin 20 mg/kg IV (max 2000 mg) at ≤50 mg/min. If still seizing → RSI & proceed to Stage 4. |
| Stage 4 | 30–60 min | Refractory SE — Critical Care. Intubate & ventilate. Transfer to ICU. Refer to neurology. | Propofol ≤4 mg/kg/hr continuous infusion and/or Midazolam 0.1–0.2 mg/kg bolus then 0.05–0.5 mg/kg/hr. Commence cEEG monitoring. Ensure pre-existing ASMs are continued. |
| Stage 5 | >60 min | Super-refractory SE — discuss with tertiary neurocritical care; consider transfer. | Optimise non-sedating ASMs. Consider thiopentone, IV ketamine, or volatile isoflurane. Add lacosamide or phenobarbitone. If autoimmune suspected: pulsed methylprednisolone 1 g/day × 3 days, IVIG, or plasma exchange. |
💊 Anti-Seizure Medication Doses (Appendix 3)
| Drug | Loading Dose | Mechanism | Key Notes |
|---|---|---|---|
| Lorazepam | 0.1 mg/kg IV up to 4 mg (1–2 mg aliquots if <50 kg or >70 yr) |
GABAA agonist (BZD) | First-line rescue. Halve dose if <50 kg. |
| Midazolam | 10 mg buccal/IV/IO (5 mg if <50 kg) |
GABAA agonist (BZD) | Alternative to lorazepam; buccal route suitable prehospital. Tachyphylaxis in prolonged use. |
| Levetiracetam | 60 mg/kg IV (max 4500 mg) in 100 mL NS/5%G over 10 min Maintenance: 1500 mg BD if CrCl >80 mL/min |
SV2A ligand — modulates synaptic vesicle exocytosis | Dose-adjust in renal impairment. Caution: depression, psychosis, agitation. No routine plasma monitoring. 1:1 IV-to-enteral conversion. |
| Sodium Valproate | 40 mg/kg IV (max 3000 mg) in NS over 10 min Maintenance: 20–30 mg/kg/day in 2–3 doses, starting 8 h after load |
Na+/Ca2+ channel blocker + GABA modulator | MHRA 2024: avoid in patients <55 yr unless no alternative (teratogenicity; male infertility). Avoid in liver disease, mitochondrial disease, porphyria. Monitor LFTs. |
| Phenytoin | 15–20 mg/kg IV (max 2000 mg) at ≤50 mg/min (10–25 mg/min in elderly/cardiac) Maintenance: 100 mg TDS IV, ≥8 h after load |
Voltage-gated Na+ channel blocker | Only licensed agent for SE. Narrow TI; non-linear PK. Monitor trough levels (target 10–20 mg/L; correct for albumin <32 g/L). Risk: arrhythmias, QT prolongation, extravasation (high pH). |
| Lacosamide | 200 mg IV loading Maintenance: 100–200 mg BD (max 400 mg/day) |
Enhances slow inactivation of voltage-gated Na+ channels | Used in RSE/SRSE. PR prolongation risk; caution in cardiac conduction disease. Dose-reduce in end-stage renal disease. 1:1 IV-to-enteral conversion. |
🏥 ICU Sedation — Refractory & Super-Refractory SE (Appendix 4)
| Drug | Induction | Continuous Infusion | Key Cautions |
|---|---|---|---|
| Propofol | 1–2.5 mg/kg IV | 1–4 mg/kg/hr (max 4 mg/kg/hr). Increase by 0.2 mg/kg/hr q2 h until EEG burst suppression. | PRIS risk at >4 mg/kg/hr (metabolic acidosis, rhabdomyolysis, cardiac failure). Check triglycerides q2–3 days; CK + ECG if dose exceeds limit. Causes hypotension. |
| Midazolam | 0.1–0.2 mg/kg IV | 0.05–0.5 mg/kg/hr (max 20 mg/hr). Increase by 0.1 mg/kg/hr q4 h. | Tachyphylaxis in prolonged sedation. Accumulates in hepatic/renal failure (active metabolite). May displace phenytoin from albumin — interpret levels with caution. |
| Thiopentone | 3–5 mg/kg IV | 3–5 mg/kg/hr (max 8 mg/kg/hr). Increase by 0.5 mg/kg/hr q6 h. | Zero-order kinetics; large Vd; long washout from adipose. 5-day wait after infusion before brainstem testing. Hypotension, rhabdomyolysis, hypokalaemia (rebound hyperkalaemia on withdrawal). |
| Ketamine | 0.5–2 mg/kg IV | 1–5 mg/kg/hr (max 7.5 mg/kg/hr). | Limited controlled data in SE. Rarely causes respiratory depression. May cause hypertension or psychiatric symptoms. NMDA receptor antagonist — useful in refractory/super-refractory SE. |
📋 Key General Recommendations
- Seek critical care review early if seizures continue after maximal benzodiazepine + 1 non-sedating ASM.
- cEEG monitoring advised for ongoing depressed consciousness, RSE or SRSE. If unavailable, use extended intermittent EEG.
- Continue all pre-existing anticonvulsant therapy at full dose throughout emergency treatment; reverse any recent reductions. Do not omit doses while awaiting drug levels.
- Neurological opinion within 24 h of ICU admission for RSE or SE of unclear cause.
- SRSE patients should be discussed with and ideally transferred to a tertiary neurocritical care unit.
- For SRSE, actively consider autoimmune encephalitis / NORSE / FIRES and involve neurology for potential immunotherapy even with negative serology.
⚠️ MHRA 2024 — Valproate Safety Update: Sodium valproate should not be initiated in female or male patients under 55 years unless there is no other effective or tolerated treatment, due to risk of teratogenicity in females and impaired fertility in males. Avoid in liver disease, mitochondrial disease and porphyria. Monitor LFTs during use.