Red flags
- Status epilepticus (>5 min or recurrent without recovery)
- Widened QRS (>100ms) with seizure - sodium channel blocker toxicity (TCA, cocaine, flecainide)
- Hyperthermia + rigidity - serotonin syndrome / NMS / sympathomimetic toxicity
- Refractory to first-line benzodiazepine + second agent
- Hypoglycaemia, hyponatraemia as the seizure driver
- Co-ingestion with cardiotoxic/QRS-widening agents
Differential by mechanism
Sodium channel blockade (-> wide QRS, seizure + arrhythmia together)
- TCAs, cocaine, local anaesthetics, flecainide, propranolol (high dose)
GABA antagonism / withdrawal
- Alcohol, benzodiazepine, barbiturate, GHB withdrawal ("rum fits" 6-48h post cessation)
- Isoniazid - depletes GABA via pyridoxine antagonism, classically refractory to benzodiazepines alone
Sympathomimetic / serotonergic excess
- Amphetamines, cocaine, synthetic cathinones
- Serotonin syndrome (SSRI/SNRI/MAOI/tramadol combinations)
Direct proconvulsant drug effect (dose-dependent, lowers seizure threshold)
- Bupropion, tramadol, venlafaxine, mefenamic acid, theophylline, quinolones, lithium toxicity, clozapine (dose-related)
Metabolic
- Hypoglycaemia (insulin, sulfonylurea, alcohol), hyponatraemia (MDMA, SSRI-SIADH, oxytocin), hypocalcaemia
Focused history
- Ingestion timing, formulation, amount, co-ingestants
- Known epilepsy vs no prior seizure history
- Psychiatric medication list, recent dose changes/additions (serotonergic combos)
- Alcohol/benzodiazepine use and last dose - withdrawal timing
- Compliance with anticonvulsants, dialysis-dependent renal failure (drug accumulation)
Focused examination
- Temperature, tone, reflexes, clonus - serotonin syndrome vs NMS (hyperreflexia/clonus vs lead-pipe rigidity/hyporeflexia)
- Pupils, mucous membranes, bowel sounds - toxidrome clues
- Post-ictal vs ongoing focal signs
- ECG immediately - QRS duration, QTc
Investigation strategy
- Glucose at the bedside first - hypoglycaemia mimics/causes toxin seizures
- VBG/lactate, UEC (Na), Ca, Mg
- ECG - QRS >100ms suggests sodium channel blockade -> bicarbonate
- Paracetamol level (routine in any deliberate self-poisoning), specific drug levels where available (lithium, anticonvulsant)
- CT brain only if focal deficit, head injury, or no clear toxic cause
Management
1. First-line - benzodiazepines
- IV lorazepam or diazepam regardless of cause
2. Avoid phenytoin
- Ineffective in most toxin-induced seizures and worsens sodium channel blockade in TCA/cocaine toxicity - use a second dose of benzodiazepine, then phenobarbitone or propofol instead
3. Specific antidotes
- Isoniazid: pyridoxine 1g IV per gram of INH ingested, or empirical 5g if amount unknown
- TCA/sodium channel blockade: IV sodium bicarbonate to narrow QRS, target pH 7.5-7.55
- Hypoglycaemia: IV glucose (+ thiamine first if alcohol use suspected)
- Hyponatraemic seizure: hypertonic saline (3%) bolus
- Serotonin syndrome: cyproheptadine if benzodiazepines alone insufficient
4. Refractory seizures
- Propofol or thiopentone infusion, ICU, consider dialysis for dialysable agents (lithium, salicylate)
Traps
- Phenytoin can worsen outcomes in sodium-channel-blocker seizures - do not reach for it reflexively
- Isoniazid seizures often fail benzodiazepines alone - give pyridoxine empirically if suspected
- Always check glucose before assuming a toxicological cause
- Alcohol withdrawal seizures - give thiamine before/with glucose to avoid precipitating Wernicke's
- A single "provoked" seizure in a patient on bupropion/tramadol still needs the dose questioned, not just anticonvulsant loading
Talk track
1. Treat first, characterise second
- "Benzodiazepines are first-line regardless of cause - glucose is checked immediately."
2. Look for the sodium-channel pattern
- "A wide QRS with seizure means I'm reaching for bicarbonate, not phenytoin."
3. Know the refractory patterns
- "Isoniazid and serotonin syndrome seizures don't respond to benzodiazepines alone - pyridoxine and cyproheptadine respectively."
8 of 8 sections written · drafted 2026-09-13