A child is admitted to hospital following a seizure.

a) List the clinical features most consistent with the diagnosis of febrile convulsions.

b) List five drugs – one from each class - most commonly used for the treatment of generalised convulsive status epilepticus in children. For each drug you have listed give the appropriate dosage and one important advantage and one important disadvantage.

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College Answer

a)
 A convulsion associated with an elevated temperature greater than 38°C.
 A child younger than six years of age.
 No evidence of central nervous system infection or inflammation.

 No evidence of acute systemic metabolic abnormality that may produce convulsions.
 No history of previous afebrile seizures.
 Generalised rather than focal.
 Short (< 15 min) rather than prolonged.
 Single rather than multiple.

b)
Benzodiazepines:

a) Diazepam – 0.1 to 0.3 mg/Kg IV over 2 – 5 minutes, maximum 10 mg per dose - or

b) Midazolam - 0.1 – 0.3 mg/kg bolus IV, can be given in an infusion 0.1 to 0.5 mg/Kg/hr.
o Advantage – rapid onset, terminates seizures under most circumstances, can be administered by other routes-IM, P/R, nasally.
o Disadvantage – excessive sedation, respiratory depression. May need airway control including intubation.

Phenytoin:

15 – 20 mg/kg IV bolus dose at rate of < 50 mg/min, 5 – 10 mg/kg maintenance daily 12 hours after.
o Advantage - preventing recurrence of SE for extended periods of time.
o Disadvantages – Slow onset of action up to 30 minutes, Hypotension, cardiovascular collapse, ataxia, nystagmus, blurred vision, and coma.

Barbiturates

– Phenobarbitone: 10 – 20 mg/Kg initially up to 40 mg/Kg if needed to control seizure activity.
o Advantage – more effective than phenytoin in controlling seizure activity.
o Disadvantage – severe respiratory depression, requires monitoring in HDU/ ICU, may require intubation and ventilation.

Thiopentone: 2 – 3 mg/kg bolus IV, repeat as needed.
o Advantage – most potent of any epileptic agent.
o Disadvantages – IV anaesthetic agent hence requires intubation and ventilation for administration, hypotension.

Propofol: 1 – 3 mg /Kg bolus, 1 – 3 mg/Kg/hour.
o Advantage – quick onset and offset.
o Disadvantage – very few studies to support its use in status epilepticus, propofol infusion syndrome at high doses, requires intubation and ventilation.

Sodium Valproate - Loading dose: 20 – 40 mg/kg followed by a continuous I.V. infusion of 1 – 5 mg/kg/hour.
o Advantages – studies showing effective in 78% cases refractory to diazepam, phenytoin and phenobarb, less sedating than barbiturates.
o Disadvantages – fatal hepatotoxicity can occur hence contra-indicated in significant hepatic impairment.

Levetiracetam – Newer anti-epileptic agent – 15 (5 – 30) mg/kg bolus dose, 25 – 50mg/kg maintenance in two divided doses.
o Advantage – very good safely profile.
o Disadvantage – Limited published data in paediatric age group.

Discussion

By the most recently attempted definition, febrile convulsions are "a seizure occurring in childhood after one month of age, associated with a febrile illness that is not caused by an infection of the central nervous system". There are actually two definitions, which differ slightly. In brief summary, these are seziures which occur in the presence of fever and in the absence of any other good reason for seizures, in an age range variably described as under 6 years, 1 month to five years, 3 months to five years, and six months to six years.

Diagnostic Criteria for Febrile Seizures

International League Against Epilepsy (ILAE) definition

Definition: "a seizure occurring in childhood after one month of age, associated with a febrile illness not caused by an infection of the central nervous system, without previous neonatal seizures or a previous unprovoked seizure, and not meeting criteria for other acute symptomatic seizures"

NIH consensus statement:

Definition: "an event in infancy or childhood usually occurring between three months and five years of age, associated with fever but without evidence of intracranial infection or defined cause for the seizure"

The Royal Children's Hospital Clinical Guidelines has a slightly different age range to both of the above, and closely resembles the college answer. Clearly, both must have the same source.

The list of criteria for the diagnosis of simple febrile convulsions:

  • Fever >38.0°
  • No history of neonatal seizures
  • No previous unprovoked seizures
  • No focal neurological features (i.e. generalised seizure)
  • Tonic-clonic seizure
  • Occurs after 6 months of age, and before the age of 6
  • Lasts less than 15 minutes
  • Occurs only once per episode of febrile illness.

The list of criteria for the diagnosis of complex febrile convulsions:

  • Fever >38.0°
  • No history of neonatal seizures
  • No previous unprovoked seizures
  • Focal seizure
  • Tonic-clonic seizure
  • Occurs after 6 months of age, and before the age of 6
  • Lasts longer than 15 minutes
  • Occurs several times within the same episode of febrile illness.
  • Incomplete recovery after 1 hour.

The college then goes on to ask for five drugs – one from each class, as well as their dose, their advantages and disadvantages. Such a question lends itself well to a tabulated answer.

Pharmacotherapy of Paediatric Status Epilepticus
Drug Class Dose Advantages Disadvantages
Lorazepam Benzodiazepines 0.05-0.1
mg/kg
Can be given as buccal, IM, PR dose
Rapid onset
 
Respiratory depression
Sedation
Need for airway control
Diazepam Benzodiazepines 0.1-0.3
mg/kg
Midazolam Benzodiazepines 0.1-0.3
mg/kg
Phenytoin Hydantoin 20mg/kg Minimal sedation
No respiratory depression
Prevents seizures over a prolonged period
Not suitable for neonates
Numerous interactions
Levels need to be monitored
Levetiracetam Racetam 5-30mg/kg Very safe
Few interactions
No need for monitoring
Relatively new agent; efficacy unproven
Sodium valproate Organic acid 20-40 mg/kg Effective in refractory cases Hepatotoxic
Levels need to be monitored
Propofol Phenol 1-3 mg/kg Quick onset and offset Respiratory depression
Sedation
Haemodynamic instability
Need for airway control
Phenobarbitone Barbiturate 10-20
mg/kg
More effective than phenytoin
Thiopentone Barbiturate 2-3mg/kg More effective than phenobarbitone
(most effective of all available agents)

Much of this information can be found it its raw untreated form in Slater's chapter on neurological emergencies in children, from Oh's Manual.

References

References

 

Oh's Intensive Care manual:  Chapter 109   (pp. 1121) Neurological  emergencies  in  children  by Anthony  J  Slater.

Waruiru, C., and R. Appleton. "Febrile seizures: an update." Archives of Disease in childhood 89.8 (2004): 751-756.

Syndi Seinfeld, D. O., and J. M. Pellock. "Recent Research on Febrile Seizures: A Review." J Neurol Neurophysiol 4 (2013): 165.

Commission on Epidemiology and Prognosis, International League Against Epilepsy. "Guidelines for epidemiologic studies on epilepsy." Epilepsia 34.4 (1993).

Freeman JM. Febrile seizures: a consensus of their significance, evaluation, and treatment. Consensus development conference of febrile seizures. 1980. National Institute of Health.  Pediatrics 1980;66: 1009–12.

Ventura, Alessandro. "From the American Academy of Pediatrics: Clinical Practice Guideline: Febrile Seizures: Guideline for the Neurodiagnostic Evaluation of the Child With a Simple Febrile Seizure." Pediatrics 127.2 (2011): 389-394.

Wright, Chanin, et al. "Clinical pharmacology and pharmacokinetics of levetiracetam." Frontiers in neurology 4 (2013).