Status epilepticus – Emergency management in children

Purpose

This document provides clinical guidance for all staff involved in the care and management of a child presenting to an Emergency Department (ED) in Queensland with status epilepticus.

This guideline has been developed by senior ED clinicians and Paediatricians across Queensland, with input from Neurology and PICU, Queensland Children’s Hospital, Brisbane. It has been endorsed for statewide use by the Queensland Emergency Care of Children Working Group in partnership with the Queensland Emergency Department Strategic Advisory Panel and the Healthcare Improvement Unit, Clinical Excellence Queensland.

Introduction

Seizures are paroxysmal and involuntary events of altered consciousness, behaviour, motor skills, sensation or autonomic function that result from abnormal rhythmic discharges of cerebral neurons.¹ The majority of seizures are convulsive (involve a change in muscle tone or activity).

Individual convulsive seizures are often broadly classified as focal or generalised, based on their degree of body involvement. Classification may aid diagnosis and direct ongoing treatment in some cases, however the management priority in all seizure types is to protect the airway and terminate the seizure.

The causes of seizures are numerous, but the majority occur in the setting of a pre-existing seizure disorder, febrile illness, central nervous system (CNS) infection, head injury, poisoning or metabolic disturbance.

Epidemiological studies typically define status epilepticus as seizures lasting greater than 30 minutes or recurring without recovery to baseline consciousness over a 30 minute period.² Given the risks associated with increasing seizure duration, for the purposes of clinical management seizures lasting greater than five minutes are defined as status epileptics.

Epidemiology

Febrile convulsions are seen in 2 – 4% of children, whereas epilepsy (an idiopathic susceptibility to recurrent seizures) occurs in about 0.5% of children.³

The incidence of status epilepticus is estimated as 10-40/100,000.

Seizures account for 1 – 2% of all ED presentations to the specialist children’s hospitals in Brisbane, of which 4 – 6% are Triage Category of 1 (assumed to be actively seizing on arrival). An Australian and New Zealand study⁴ found that in children presenting with ongoing seizure activity for greater than 10 minutes, the median pre-hospital seizure duration was 45 minutes. Almost half of these had received anticonvulsant treatment by a parent, carer or ambulance officer. This suggests that children who present with ongoing seizures to the emergency service are likely to already be in established (and possibly refractory) status epilepticus and highlights the emergent need to rapidly terminate their prolonged seizures to minimise adverse events.

Assessment

History

History taking should include information on:

• details preceding the seizure including:
  • prior events and behaviour of the child
  • signs or symptoms of illness including fever
• details of the seizure including:
  • how it started
  • estimated duration
  • pre-hospital treatment
• any previous seizures and family history of seizures
• if relevant, previous seizure management including ketogenic diet
• medical and surgical history including intracranial infection or severe metabolic disturbance such as hypoglycaemia or electrolyte disturbance, neurological damage, neurosurgical procedures (including the placement of ventriculo-peritoneal shunts)

Examination

Emergency assessment and management should always involve a rapid primary survey with evaluation of (and immediate management of concerns with) airway, breathing, circulation and disability (ABCD).

Seek urgent senior emergency/paediatric advice as per local practice for a child with status epilepticus who has received two doses of benzodiazepines pre-hospital.

Consider seeking senior emergency/paediatric advice as per local practice for child with status epilepticus who has received a single dose of benzodiazepine prior to arrival.

Differential diagnoses

Other neurological conditions can present with altered level of consciousness and abnormalities of tone, posture or movement and need to be differentiated from convulsive status epilepticus. A careful history and examination will usually distinguish between these conditions. Diagnosis of an epileptic seizure should not be based on the presence or absence of single features.

Investigations

Other investigations are usually directed by history and examination findings.

Management

Refer to flowchart [PDF 1445.82 KB] for a summary of the emergency management and medications for children presenting with status epilepticus.

The goals in the emergency management of status epilepticus are to maintain vital functions whilst stopping the seizure as soon as possible and to identify and treat any underlying cause.⁵

Monitor the frequency, duration and type of seizures using the seizure chart [PDF] (QH only).

First-line agents – benzodiazepines

Benzodiazepines work by binding to GABA (gamma-aminobutyric acid) receptors in the central nervous system, which in turn hyperpolarises the neuronal membrane making it more difficult for the neuron to be activated.⁶ Midazolam and Diazepam are the benzodiazepines routinely used in the management of status epilepticus.

Midazolam

• rapid onset with anti-seizure effect often observed within one minute of IV administration⁷
• second dose is recommended if seizures are continuing five minutes after first dose
• more effective than Diazepam
• can be given reliably via the buccal, intranasal, IM, IV, or IO routes with IM the least reliable route for absorption
• oral absorption much less reliable
• buccal (or intranasal) Midazolam has largely replaced Diazepam PR for the management of seizures by parents and caregivers^3,8
• short duration of action – children who stop convulsing after an initial Midazolam dose may require a repeat dose to maintain seizure control⁶

Diazepam

• rapid onset of action with median anti-seizure effect seen within two minutes of IV administration^3,9
• second dose is recommended if seizures are continuing five minutes after first dose
• can be given via the PR, IV or IO routes
• oral absorption is effective however usually not appropriate in a child with ongoing seizure activity
• long elimination half-life but only a relatively short-lasting anti-seizure effect of between 15 – 30 minutes

Second-line agents

Second-line agents are recommended if seizure continues despite appropriate doses of first-line agents. These drugs have a longer duration of action compared with first-line agents. The choice of second line antiseizure medication in status epilepticus is now broader. The clinician may choose one based on a number of factors, including patient diagnosis, previous response to therapy, current treatment, and expected side effects (e.g. phenobarbitone and sedation).

Seek urgent senior emergency/paediatric advice as per local practice for a child with ongoing seizures despite the administration of two doses of a first-line agent.

Levetiracetam IV (Keppra)

Levetiracetam IV is a new agent which appears to be effective in terminating seizures which are not responsive to benzodiazepines and Phenytoin. A number of studies have shown its safety and efficacy in terminating refractory status epilepticus thereby avoiding intubation and ventilation.¹² It can be infused over five minutes and appears to have no acute side effects relating to hypotension or respiratory depression and no known drug interactions.

* LAM restriction: Unrestricted. Use in status epilepticus is off-label. Document informed consent (CHQ off-label medicine use consent available here: https://qheps.health.qld.gov.au/__data/assets/pdf_file/0020/714260/658998_v1.00_082020.pdf [PDF]

Phenytoin

Phenytoin is a suitable second-line agent in children aged greater than one year.

Phenobarbitone

A suitable second-line agent in:

• infants (up to one year)
• children with contraindication to Phenytoin
• children already on maintenance Phenytoin therapy

Seek urgent paediatric critical care/neurology advice (onsite or via RSQ) for a child who is continuing to have seizures following administration of second-line agent.

Newer agents

A number of anticonvulsants used as either first or second-line agents in the treatment of convulsive status epilepticus in other parts of the world may be given on advice from a paediatric neurologist.

Lorazepam (Ativan)

Lorazepam is the benzodiazepine of choice as a first-line agent across North America, UK and Europe. Lorazepam has rapid infiltration (one to two minutes after IV injection) across the blood-brain barrier and a relatively long half-life with an effective duration of action of four to six hours. It also has fewer side effects than other benzodiazepines, in particular respiratory depression.¹⁴ One small quasi-randomised trial (the only trial in a Cochrane review) found Lorazepam IV superior to rectal diazepam.¹⁵ A recent large well conducted paediatric emergency based RCT comparing Lorazepam IV to Diazepam IV found no benefit from Lorazepam either in effectiveness in termination of seizures or reduction in side effects.¹⁶

* Non-LAM medication for these indications. Needs individual patient approval before use unless local blanket approval in force. May not be available on imprest for immediate use.

Lorazepam can be administered via several routes including buccal, rectal and intranasal. It is available in Australia through a Special Access Scheme for rapid tranquilisation for patients with acute agitation and disturbed behaviour.

Valproate IV (Epilim)

Valproate IV is currently being used in a number of centres across the world as either a second line agent or a third line agent. Multiple small case series have been published, however no prospective randomized control trial for children in convulsive status epilepticus currently exists. A number of adult studies have shown that 60 – 80% of seizures not responding to benzodiazepines and Phenytoin will cease with administration of Valproate IV.^17,18 It does not appear to have significant adverse effects acutely with stable haemodynamic parameters following administration. Valproate IV is less frequently used in children due to the risk of hepatotoxicity in infants and young children or those with underlying metabolic condition.

* LAM restriction: For status epilepticus in adults; and in children (if used as per this guideline). Use in status epilepticus is off-label. Document informed consent (CHQ off-label medicine use consent available here: https://qheps.health.qld.gov.au/__data/assets/pdf_file/0020/714260/658998_v1.00_082020.pdf [PDF]. This product is also LAM listed for maintenance treatment of epilepsy when oral sodium valproate is an established therapy, but the patient’s condition prevents oral administration.

Specific (rare) treatable causes of status epilepticus

Treatment for the following may be given on advice from a paediatric neurologist:

• pyridoxine responsive seizures (treat with Pyridoxine 30 mg/kg by IV or IM injection*)
  *Non-LAM medication for these indications. Needs individual patient approval before use unless local blanket approval in force. May not be available on imprest for immediate use.
• thiamine deficiency (treat with Thiamine IV 100mg – NOT dose/kg)
• hyperammonaemia (test requires EDTA tube on ice to lab and verbal request)
• hyponatraemia (see Hyponatraemia guideline [PDF 579.65 KB])
• hypomagnesaemia (see Magnesium Sulfate IV Medication Guideline [PDF] (QH only))
• lignocaine toxicity (lipid rescue) (see Local Anaesthetic Systemic Toxicity guideline

Rapid sequence induction and intubation

• a sequence of events designed to safely and quickly protect the airway and breathing of severely ill children to maintain oxygenation to the brain and vital organs.
• allows the use of larger doses of anti-epileptic medications whose primary adverse effects are hypoventilation and apnoea (e.g. benzodiazepines and barbiturates).
• facilitates the investigation (e.g. CT), treatment and management of causes of status epilepticus.

Paralysis and Sedation (Induction)

Seek urgent paediatric critical care advice (onsite or via RSQ) for a child with status epilepticus requiring intubation.

Paralysis will lead to apnoea and is painful in awake individuals and therefore should follow induction with a sedation and analgesic agent.

Specific considerations around RSI/choice of agents in child with status epilepticus

Thiopentone or Propofol are suitable induction agents in status epilepticus as both medications are effective anticonvulsants when given as a bolus dose for induction. Caution is required in hypotensive patients; however, blood pressure is often high, and Thiopentone or Propofol usually well tolerated in the setting of status epilepticus. Cochrane reviews have not found any evidence that outcomes with Propofol are better or worse than Thiopentone.¹⁹ Recent research suggests that Ketamine may have antiepileptic effects and may be an appropriate induction agent in haemodynamically unstable patients.

For status epilepticus, Rocuronium appears to be the drug of choice when available. Historically Succinylcholine (Suxamethonium) has been the most commonly used neuromuscular blocking agent due to its rapid onset (15 – 30 seconds) and short duration of action (5 – 10 minutes). Suxamethonium has an increased risk of causing life-threatening malignant hyperthermia (MHT), particularly in children with neuromuscular diseases, some of whom will present with seizures. Rocuronium is another agent that also has rapid onset (30 – 60 seconds) and is not associated with MHT but has a longer duration of action (30 – 60 minutes). Sugammadex is an antidote allows the safe reversal of paralysis due to Rocuronium if required.

Children requiring special consideration

Ketogenic diet

Some children with seizures are managed successfully on a ketogenic diet which often takes many weeks to stabilise. Glucose administration may negate the ketogenic diet and administration should be avoided unless they are hypoglycaemic. Consult with the Ketogenic Diet treating team or your local Paediatrician.

Vagal nerve simulators

Seek specialist advice in child with vagal nerve simulators as may affect management (may need to be switched off during anaesthesia, may trigger bradycardia if damaged by external defibrillation and contraindication for MRI).

Escalation and advice outside of ED

Clinicians can contact the services below if escalation of care outside of senior clinicians within the ED is needed, as per local practices. Transfer is recommended if the child requires a higher level of care.

Critically unwell or rapidly deteriorating child

Non-critical child

Inter-hospital transfers

Disposition

When to consider discharge from ED

Seek senior emergency/paediatric advice as per local practice prior to discharge for a child who has experienced status epilepticus.

Children for whom this is the first episode of status epilepticus are usually admitted for a period of observation. Discharge may rarely be considered for children who did not require administration of second-line agents for seizure control providing that:

• diagnosis of seizure is certain
• no further seizures after a period of observation for several hours
• child is alert and responding normally
• all observations (including GCS, pupil reaction, BP, Pulse Rate) are within normal ranges
• carers have been educated on the management of a subsequent seizure
• parents/caregivers are able to safely manage the child at home, return promptly in the event of deterioration/another seizure

Rarely, children may be discharged on Midazolam. This must only be done in consultation with Paediatric or Paediatric Neurology staff. If so, caregivers must receive education on its administration prior to discharge. This should be documented in medical record.

On discharge, caregivers should be provided with:

• Discharge letter for family and GP +/- specialist referral
• Seizures – First Aid Factsheet

Follow-up

Depends on seizure type (first or subsequent seizure, febrile or afebrile seizure, focal or generalised seizure) and whether episode represents a change in seizure control.

Discuss outpatient follow-up plan with local paediatric service. Refer to paediatrician/neurologist if urgent otherwise ask GP to arrange specialist referral.

When to consider admission

The majority of children with status epilepticus will require admission to an inpatient service. Admission to a SSU (where relevant) may be considered for a child in whom seizures have ceased following administration of first-line agents but require a further period of observation prior to discharge.

Related documents

Guidelines

• Refractory Status Epilepticus Management in Children [PDF] (QH only)

Factsheet

• Seizures – First Aid Factsheet