Paediatric Intensive Care Unit

Guideline for Management of Acute Seizures and Status Epilepticus in Infants and Children

1. Aims
2. Introduction
3. Definitions
4. Aetiology of status epilepticus in children
5. Systemic complications
6. Initial management
7. Basic investigations
8. Further investigations
9. Other investigations to consider
10. Management of refractory status epilepticus
11. Antibiotics and antivirals

• Appendix 1: Initial Treatment Algorithm for Status Epilepticus in Infants and Children
• Appendix 2: Flow chart

1. Aims

This document is aimed at medical and nursing staff on the Paediatric Intensive Care Unit (PICU) looking after patients with acute seizures who are referred or admitted to the PICU. It should be used for management of prolonged (or repetitive) generalised or focal, clonic or tonic-clonic seizures. The treatment of any other type of seizure should be discussed with a consultant paediatric neurologist.

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2. Introduction

Convulsive status epilepticus is a life-threatening condition with serious risk of neurological sequelae or death. The reported mortality rates of status epilepticus in children vary from 3 to 9%, with underlying aetiology as the main predictor.

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3. Definitions

Convulsive status epilepticus (SE) is traditionally defined as a clonic or tonic-clonic seizure lasting more than 30 minutes, or repeated seizures occurring over a 30-minute period without recovery of consciousness between each convulsion. Some studies have suggested that the definition should include patients with seizures of a shorter duration, such as 10 minutes. For the purpose of treatment decisions, this shorter definition has merit. Convulsive seizures lasting more than 5 to 10 minutes have a higher risk of lasting 30 minutes or more, and treatment delay is associated with delayed response to treatment. Extensor posturing is a sign of brain herniation until proven otherwise.

Refractory SE is that which persists for longer than 60 minutes despite appropriate treatment with benzodiazepines, phenytoin and phenobarbitone. The outcome in terms of morbidity and mortality is worse with more prolonged seizures.

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4. Aetiology of status epilepticus in children

25% are complex febrile convulsions (this is usually a retrospective diagnosis)
25% are remote symptomatic (children with prior neurological abnormality)
25% are idiopathic epilepsy
25% are acute symptomatic requiring specific treatment

• Traumatic brain injury, including non accidental injury
• CNS infection: meningitis, encephalitis, cerebral abscess, empyema
• Encephalopathy: metabolic disease, poisoning, electrolyte disturbance
• Space occupying lesion (tumour, haematoma or blocked shunt)
• Acute hypoxic ischaemic insult
• Cerebrovascular event
• Sudden withdrawal of anti-epileptic drugs in child with epilepsy

New onset tonic seizures in a child with a shunt may indicate raised intracranial pressure. In this situation, sedative drugs may be harmful. Discuss this situation early with a senior colleague and neurosurgeon.

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5. Systemic complications

These contribute to morbidity and mortality related to SE and include:

• Hypoxaemia
• Lactic acidosis or respiratory acidosis
• Hypo/hyperglycaemia, hyponatraemia, hypo/hyperkalaemia
• Blood pressure disturbances
• Raised intracranial pressure
• Rhabdomyolysis and acute kidney injury
• Consumptive coagulopathy
• Multi organ failure

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6. Initial management

• Follow initial APLS treatment algorithm (appendix 1)
• *In children with known epilepsy check if there is a personalised emergency care plan* specific to the child on PPM+ or held by their parent/carer. Ask if they are already on levetiracetam, phenytoin or phenobarbitone, as this will influence the choice of drugs given.
• Treat hypoglycaemia
• If giving phenytoin use correct giving set, monitor for hypotension and cardiac arrythmias
• Do basic investigations (section 7)
• Consider whether there may be an acute symptomatic aetiology which requires further investigation (section 8) and urgent treatment
• Early involvement of anaesthetic team to prepare for intubation and ventilation if needed
• Discuss with consultant paediatrician and PICU

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7. Basic Investigations

• Blood sugar
• Blood pressure (to exclude hypertensive encephalopathy as primary cause)
• FBC, CRP, U&Es, calcium, magnesium, LFTs, blood culture
• Check anti-epileptic drug levels if on treatment for epilepsy

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8. Further investigations

Urgent CT brain may be needed to exclude space occupying lesions such as tumour, bleed or abscess. Ask for CT with contrast if meningitis or abscess is suspected. Remember that a normal CT scan does not rule out the possibility of raised intracranial pressure.

Arrange an urgent CT scan if any of the following are present:

• Any child with SE when aetiology is unknown
• Focal neurological signs including focal seizure
• Asymmetric or unreactive pupils
• Clinical suspicion of raised intracranial pressure
• Reduced conscious level 1 hour post seizure
• History of trauma
• Hydrocephalus with VP shunt in situ
• Suspicion of abusive head trauma

Lumbar puncture is not necessary during the acute stage and will not change immediate management. Send for MC&S, protein, glucose, meningococcal PCR and herpes PCR.  Don’t forget to do blood glucose at the same time.
Indications for LP

• age <12 months
• suspicion of meningitis or encephalitis; consider LP in all children presenting with first episode of febrile convulsive status epilepticus (and have low threshold for discussing with a consultant neurologist)

Relative contradindications to LP *

• Glasgow Coma Score <13
• Other signs of raised intracranial pressure (altered pupillary responses, absent Doll’s eye reflexes, decerebrate or decorticate posturing, abnormal respiratory pattern, papilloedema, hypertension, bradycardia)
• Within 30 minutes of a convulsive seizure
• Focal seizures or new focal neurological signs
• Tonic seizures (beware extensor posturing - this is a sign of brain herniation until proven otherwise)
• Clinical evidence of systemic meningococcal disease or shock
• Local infection over the LP site
• Coagulopathy, low platelet count or anticoagulant treatment
• If CT scan shows focal lesion such as subdural empyema, brain abscess, focal infarct / bleed, hydrocephalus, or features suggestive of raised intracranial pressure

* If a relative contraindication is present, LP should not be undertaken without discussion with a PICU consultant.

EEG should be requested if there is:

• Unexplained SE in any child
• Refractory SE
• Focal seizures
• Possible non convulsive status or sub clinical status epilepticus

Other investigations to consider:

1. Mycoplasma serology (acute and convalescent)
2. Viral serology
3. Swab any skin lesions (especially in neonates)
4. Urine toxicology
5. Blood lead level, blood film
6. Metabolic investigations (consider if history of consanguinity, or previous family history of metabolic disease or unexplained death. If high suspicion, then discuss at an early stage with a metabolic consultant or a paediatric neurologist).
   • Blood gas
   • Biotinidase level
   • Serum ammonia and lactate
   • Urine amino acids and organic acids, serum amino acids

Discuss with a consultant neurologist who will advise whether the following are indicated:

• IL-6, neurotransmitters, oligoclonal bands
• NMDA/LGI1/CASPR2/anti-MOG/AMPA 1&2/GABA A&B receptor antibodies
• Microarray, whole genome sequencing, R14

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9. Management of refractory status epilepticus

• Discuss with consultant paediatric intensivist and neurologist.
• Consider continuous cerebral function monitoring.
• IV phenobarbitone 20mg/kg loading dose. Infuse over 30 minutes.
• IV midazolam. Start with a bolus of 100microgram/kg plus a continuous infusion at 2microgram/kg/min. Reassess every 15 minutes. If no response then give a further bolus, before increasing by 2 microgram/kg/min. Repeat until response seen, up to a maximum of 20 microgram /kg/min.
• IV thiopentone 2mg/kg bolus in neonates or 4mg/kg in children over 1 month of age. Continuous infusion dose 2-8 mg/kg/hr to induce burst suppression for 24 to 48 hours. Must be done with cerebral function monitoring and under consultant supervision. Patient may require inotropic support.
• For unexplained refractory SE in neonates and infants start pyridoxine 30mg/kg/day and send urine α-amino adipic semialdehyde (can start treatment before taking sample). Do not switch to pyridoxal-5-phosphate until after neurotransmitters sent.
• Consider folinic acid (calcium folinate) 15mg once daily in neonates – only after discussion with neurologist and once neurotransmitters have been sent.
• Consider biotin 10mg once daily in neonates after discussion with a neurologist or metabolic consultant (can start treatment before taking biotinidase level).
• Do not start steroids without discussion with consultant neurologist.

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10. Antibiotics and antivirals

Cefotaxime for any child in whom CNS infection cannot be excluded, all seizures >30 min, complex febrile seizures.
Have a low threshold for giving acyclovir (for herpes simplex encephalitis) and clarithromycin (for mycoplasma encephalitis). Acyclovir should be given to any child with a first or unexplained febrile SE until herpes simplex encephalitis is excluded.
Acyclovir and clarithromycin should both be added if:

• History of prodromal illness that may suggest encephalitis: fever, altered consciousness, behavioural changes, or history of recent herpes infection
• Focal neurological signs including focal seizures
• Any neonate (<28 days of age) presenting with seizure or reduced conscious level of unknown cause

Please refer to the BNF for Children for guidance on drug dosing.