A registrar-level reference: the pathophysiology that drives the algorithm, why each drug is chosen, and management of the actively-seizing child, the first seizure, and febrile seizures — in ED and on the ward.
Read first. Decision-support, not a substitute for senior/PICU/neurology input or your local Metro South protocol. Confirm every drug dose against CREDD / the current CHQ flowchart / local formulary before administration. Doses here follow the CHQ statewide status epilepticus guideline (CHQ-GDL-60014). Escalate early — status epilepticus is a time-critical neurological emergency.
⚡ Child actively seizing > 5 min? Go straight to the timed ED algorithm. Jump to §4 →Epidemiological studies once defined status at 30 minutes, but for clinical management the trigger is 5 minutes — because that is when spontaneous termination becomes unlikely, drug response starts to fall, and the window to prevent neuronal injury is closing.
An Australasian study found children who present still seizing have a median pre-hospital duration of ~45 minutes, and nearly half have already had a benzodiazepine. Assume the child in front of you is in established (possibly refractory) status — count pre-hospital doses, and don't restart the clock at the ED door.
A seizure is a failure of the balance between excitation (glutamate acting on NMDA/AMPA receptors) and inhibition (GABA acting on GABA-A receptors). Normally inhibitory mechanisms terminate a seizure within a minute or two. In status, those mechanisms fail — and the failure is progressive and molecular.
Within minutes of a sustained seizure, inhibitory GABA-A receptors are internalised (pulled off the synaptic membrane), while excitatory NMDA receptors are recruited to it. Inhibition falls, excitation rises, and the seizure becomes self-sustaining. Because benzodiazepines work through GABA-A receptors, their efficacy falls as those receptors disappear — this is time-dependent pharmacoresistance, and it is why an early benzo works and a late one may not.
Persistent glutamate/NMDA activity drives Ca²⁺ influx and excitotoxic neuronal injury. Early on, cerebral blood flow rises to meet demand (compensated); after ~30 min this decompensates — hypoglycaemia, hyperthermia, lactic acidosis, hypoxia, hypotension, rhabdomyolysis — amplifying brain injury.
Three clinical rules fall straight out of the biology: (1) treat early — the benzo window closes fast; (2) escalate promptly — don't give a third benzo, move to a second-line agent that works by a different mechanism (Na-channel, SV2A, GABA-duration); and (3) in refractory SE, NMDA antagonism becomes attractive — this is the rationale for ketamine, which targets the up-regulated excitatory receptors that benzodiazepines can no longer reach.
Most seizures occur with a pre-existing seizure disorder, febrile illness, CNS infection, head injury, poisoning or metabolic disturbance. Classify as provoked (acute symptomatic) vs unprovoked — it changes work-up and recurrence risk.
| Category | Causes |
|---|---|
| Provoked — metabolic | Hypoglycaemia, hyponatraemia, hypernatraemia, hypocalcaemia, hypomagnesaemia, inborn errors of metabolism, uraemia, hyperammonaemia |
| Provoked — infective | Febrile seizure (commonest), meningitis, encephalitis (incl. HSV), cerebral malaria, sepsis-associated |
| Provoked — toxic | Isoniazid (→ pyridoxine), tricyclics & Na-channel blockers, sympathomimetics, local anaesthetic (LAST), theophylline, drug/benzodiazepine withdrawal |
| Provoked — structural / vascular | Trauma & non-accidental injury, ischaemic/haemorrhagic stroke, hypoxic-ischaemic injury, hypertensive encephalopathy, VP-shunt malfunction |
| Provoked — immune | Anti-NMDA-receptor & other autoimmune encephalitis, ADEM |
| Unprovoked | Epilepsy syndromes, structural (cortical malformation, tuberous sclerosis, tumour), genetic (e.g. SCN1A/Dravet), remote symptomatic (old CNS injury) |
| Age | Think first of |
|---|---|
| Neonate | Hypoxic-ischaemic encephalopathy (commonest), infection (incl. HSV), metabolic (hypoglycaemia, hypocalcaemia, hyponatraemia), inborn errors, stroke/ICH, pyridoxine-dependent, benign familial. Often subtle — phenobarbitone remains first-line. |
| Infant / toddler | Febrile seizure, infection, non-accidental injury, metabolic, epilepsy onset (incl. Dravet — avoid Na-channel blockers). |
| Child | Febrile (up to 6 yr), idiopathic epilepsy syndromes, CNS infection, trauma. |
| Adolescent | Idiopathic generalised epilepsy, non-adherence with medication, toxins/recreational drugs & withdrawal, first presentation of structural lesion. |
Glucose in everyone. Then, as directed: Na⁺, Ca²⁺, Mg²⁺ (especially infants and prolonged seizures), pyridoxine deficiency (refractory infant seizures), and toxins. A seizure that won't stop despite correct drug escalation is a prompt to re-hunt for one of these — a benzodiazepine will not fix hyponatraemia or hypoglycaemia.
Goal: maintain vital functions while stopping the seizure as fast as possible, and find the cause. Aim to terminate any seizure needing a second-line agent within 30 minutes. Count pre-hospital benzodiazepine doses toward the two-dose limit.
| Drug | Mechanism | Dose (CHQ) | Why / caution |
|---|---|---|---|
| Midazolam | GABA-A positive allosteric modulator → ↑ frequency of Cl⁻ channel opening → hyperpolarisation | 0.15 IV/IO · 0.3 buccal/IN · 0.2 IM mg/kg (max 10) | Fast, multi-route, first-line. Respiratory depression with repeat dosing. |
| Diazepam | As above | 0.1–0.4 IV · 0.3–0.5 PR mg/kg | Short anti-seizure duration (15–30 min). Never IM. |
| Lorazepam | As above | 0.05–0.1 mg/kg IV (max 4) | First-line in UK/US; longer action. No benefit over diazepam in RCT; limited AU availability. |
| Levetiracetam | Binds SV2A synaptic-vesicle protein → modulates neurotransmitter release | 60 mg/kg IV (max 4.5 g) over 5 min | No significant hypotension/resp depression, no major interactions — safest fast second-line. |
| Phenytoin | Voltage-gated Na⁺-channel blockade (stabilises inactivated state) → limits repetitive firing | 20 mg/kg IV (max 1.5 g) over ≥20 min | Arrhythmia/hypotension → cardiac monitor, slow, not with glucose. Contraindicated in Dravet. |
| Phenobarbitone | Barbiturate — GABA-A agonist (↑ duration of Cl⁻ opening; direct at high dose) | 20 mg/kg IV (max 1 g) over ≥20 min | First-line in neonates/infants. Sedation & resp depression, esp. with benzodiazepines. |
| Sodium valproate | Multi-modal: ↑GABA, Na⁺ & T-type Ca²⁺ modulation | 40 mg/kg IV (max 3 g) over 3–5 min | Preferred >2 yr. Hepatotoxicity — avoid <2 yr & suspected metabolic/mitochondrial disease. |
| Ketamine | NMDA-receptor antagonist — targets up-regulated excitatory receptors in established SE | Critical-care directed | Useful in refractory SE & haemodynamic instability (maintains BP). |
| Thiopentone / propofol | GABAergic anaesthetics with intrinsic anticonvulsant activity | RSI induction (critical care) | Effective for RSI in SE. Propofol-infusion-syndrome caution in children. |
| Rocuronium | Non-depolarising neuromuscular blocker | RSI paralysis | Preferred over suxamethonium (no MH risk; sugammadex reversible). |
| Pyridoxine (B6) | Cofactor for glutamate decarboxylase → GABA synthesis | 30 mg/kg IV/IM | Pyridoxine-dependent epilepsy — consider in refractory neonatal/infant seizures. |
Benzodiazepines boost failing inhibition (works early, fails late as GABA-A receptors internalise); second-line agents attack excitation by a different route (Na-channel / SV2A / prolonged GABA); anaesthetic agents shut the cortex down; and ketamine blocks the excitation that has taken over. Escalate through mechanisms, not by repeating the same one.
A seizure on the ward runs the identical timed pathway — the differences are that you often know the child and their plan, and you must bring the resources to the bedside fast.
Once the child has stopped seizing, the assessment answers two questions: (1) Was it actually a seizure? and (2) Is it a symptom of something treatable? Acute symptomatic causes are commonest under 6 months.
Point toward seizure: aura, tongue-biting, a clear post-ictal period, occurrence in sleep, Todd's paresis. Point toward syncope: pre-event pallor/sweating, upright/prolonged standing, rapid recovery.
| Test | When & why |
|---|---|
| Blood glucose | All children, immediately — a seizure may simply be hypoglycaemia. |
| Electrolytes ± Ca/Mg | <12 months, prolonged seizure or one needing a second-line agent, not back to baseline, comorbidity (metabolic/diabetes/dehydration), or clinical suspicion. Low yield in a well >12-month-old who has fully recovered. |
| ECG | If the event could be syncopal/cardiac or there's a family history of sudden death — look for long QT, Brugada, HCM (dagger Q), pre-excitation (short PR + delta). |
| Lumbar puncture | Suspected meningitis/encephalitis or SAH — only once returned to neurological baseline. |
| Toxicology | If ingestion/toxidrome suspected — assay guided by the agent. |
| Neuroimaging | Urgent CT/MRI: persistent altered consciousness, new focal signs/?stroke, ?intracranial bleed, third-line drug needed, <6 months, raised ICP, recent trauma, anticoagulant/coagulopathy. Otherwise MRI is the test of choice, usually outpatient (esp. new focal seizures or onset <2 yr). |
| EEG | Not acutely for a controlled seizure. Helps classify syndrome & guide prognosis; arrange via the paediatric team, generally after discussion — NICE suggests after a second seizure, or after the first following specialist discussion. |
Anti-epileptic drugs are not usually started after a first unprovoked seizure — only by the paediatric team, with counselling, when recurrence risk is high. Every child needs safety advice (supervised bathing/showering & swimming, heights, cycling, no driving if of age) and urgent (category-1) outpatient follow-up — a diagnosis of epilepsy is made by a specialist, not in ED. Admit if <6 months, prolonged seizure/SE, incomplete recovery, focal seizure, developmental delay, or comorbidity.
Occur in ~3% of children, 6 months–6 years, peak 12–18 months. Simple febrile seizures don't cause brain damage and don't in themselves mean epilepsy. The work-up targets the source of fever, not the seizure.
| Type | Definition |
|---|---|
| Simple | Fever + ALL: generalised tonic-clonic, <15 min, does not recur within 24 h / same illness, no afebrile-seizure history, no neuro abnormality or CNS-infection/metabolic features. |
| Complex | Fever + ANY: >15 min, focal features, or recurs within 24 h / same illness. → seek senior advice. |
| Febrile status | Fever + seizure >30 min (or repeated without regaining consciousness). |
| Benign seizure w/ gastroenteritis | Neurologically normal child 2 mo–6 yr, afebrile GE, no dehydration/electrolyte disturbance. |
ConSEPT (PREDICT, Australia/NZ, 2019) & EcLiPSE (UK, 2019): head-to-head levetiracetam vs phenytoin as second-line. Levetiracetam was not superior — but was comparably effective and, given its ease of use and safety, is a reasonable first-choice second-line.
ESETT (US, incl. children, 2019–20): levetiracetam, valproate and fosphenytoin were equally effective (~50%) with no difference in safety — so any of the three is a legitimate first-choice second-line, and the decision is individualised.
Benzodiazepine first-line is the one part supported by strong RCT evidence; buccal/intranasal midazolam is as effective as and more practical than rectal diazepam, and midazolam beats diazepam overall.
| Element | QLD / CHQ | RCH Melbourne |
|---|---|---|
| Framework | APLS-style timed algorithm, 5-min steps | APLS-style timed algorithm, ~10-min steps |
| First-line | Midazolam 0.15 IV / 0.3 buccal-IN / 0.2 IM mg/kg; ×2 max | Same benzodiazepine approach |
| Levetiracetam dose | 60 mg/kg (max 4.5 g) — aligns with ESETT | 40 mg/kg (max 3 g) — aligns with ConSEPT/EcLiPSE |
| Phenytoin / phenobarb | 20 mg/kg each | 20 mg/kg each |
| Valproate | 40 mg/kg; preferred >2 yr | Listed as an option |
| Refractory | RSI (thiopentone/propofol/ketamine + rocuronium) + PICU/RSQ | RSI + PICU; equivalent principles |
Both are APLS-derived and clinically equivalent in structure; the visible difference is the levetiracetam dose (60 vs 40 mg/kg). Follow whichever protocol governs your site, and confirm against the current flowchart.
Most senior resource onsite — paediatric critical care / anaesthetics / paediatrics — for airway & refractory SE.
Paediatric critical care & neurology advice; retrieval of the unstable child. Notify early.
QCH advice, disposition & transfer (24 h).
Paediatric videoconference support (24 h).