While many of the causes and types of seizures in children are similar to adults, some differences exist in etiologies, manifestations, and responses to antiepileptics. Many of these differences are accounted for by factors related to the developing brain of a child.1 For example, certain considerations with respect to seizure are unique to children, such as febrile seizure and factors related to underlying metabolic disease, genetic predisposition, or neurovascular anatomy. Other factors unique to children are trauma (non-accidental) and ingestion. This article is written as a pediatric supplement to a recent ACEP Now article entitled, “Tips for Managing Active Seizures in the Emergency Department” by Anton Helman, MD, CCFP(EM), FCPP. 

Seizure is one of the most common neurologic emergencies in children.2 For a parent, witnessing a child’s  seizure can be distressing and therefore a call to 9-1-1 may ensue. Status epilepticus (currently defined as a seizure that lasts more than five minutes, or a series of two or more shorter seizures without return to baseline) is a true medical emergency.3 The definition of status epilepticus (International League Against Epilepsy) was recently modified to highlight the recent understanding that irreversible neurologic damage occurs faster than previously thought and for the purpose of intervening urgently, the previous duration of 15 minutes was shortened to five minutes. For this reason, refractory seizure, which is associated with irreversible neurologic damage, is defined as convulsive seizure lasting more than 30 minutes.3

Similar to adults, the most common emergency department (ED) presentation of status epilepticus is convulsive type (also known as tonic-clonic type). Seizures lasting more than 30 minutes have been associated with poor outcomes, higher likelihood of complications, and are considered refractory. Children younger than two years old and those with febrile seizures are at greater risk for status epilepticus. Most causes of status epilepticus remain unknown, however, febrile seizure is likely the most common cause of status epilepticus in children six months to five years.^{4, 5}

The goal of therapy is to stop seizures as quickly as possible, because the longer the seizure continues the more challenging it becomes to stop it successfully.6  In addition to this, prevention of recurrence is also a desired goal.6

Considerations for Pediatric Seizures:⁷ 

• Duration of seizure
• Type of seizure (convulsive or non-convulsive)
• Preceding intervention (e.g., rectal diazepam administered by parent/caregiver or medication administered by prehospital providers)
• Any prior seizure history
• Presence of fever within the previous 24 hours of the seizure
• Any medical history that increases seizure risk
• Trauma or possible ingestion
• Electrolytes (glucose, calcium, sodium, and magnesium)
• Presence of hypo- or hyperthermia

Attention to potential underlying cause of seizure is an important part of seizure management.⁷ In children, ingestion and trauma (intentional or accidental) also need to be considered. In smaller children, undiagnosed metabolic disease and structural brain abnormalities should also be considered. 

Pre-Hospital Management of Seizure

Ability to support the airway and administer medications is of critical importance. Therefore, most seizure transport is provided by an advanced life support unit. Pre-hospital personnel have protocols that allow for use of these first-line agents en route to the ED.⁸ Early use of appropriate medication, such as a benzodiazepine, results in the most favorable outcomes.⁹ If quick intravenous access is not possible, a typical dose of benzodiazepine may be given via intramuscular (IM) or intranasal (IN) routes.⁹ A dose of midazolam (Versed) 0.1–0.2 mg/kg IM (maximum dose 4 mg) or IN 0.2 mg/kg (maximum dose 4 mg) can be given prior to ED arrival.^{9, 10} The higher intranasal dose is to account for incomplete absorption of the dose through nasal mucosa. Lorazepam (Ativan) and diazepam (Valium) may not be as effective if given IM due to slow onset of action and delay in seizure termination.¹¹ 

Airway adjunct consideration depends on assessment of the patient airway and may include supplemental oxygen and placement of oral or nasal airways. 

ED Management of Status Epilepticus in Children 

First-line agents: A child who continues to seize upon ED arrival, will be given additional doses of benzodiazepine to stop the seizure. The choice of benzodiazepine agent depends on whether an intravenous access is present. Both in pre-hospital and in hospital settings, midazolam is the first choice if IM or IN route is chosen. If an intravenous line is present, lorazepam 0.1 mg/kg is an appropriate alternative and may be slightly preferred to midazolam for its longer duration of action. However, due to depot effect and slower onset of action, lorazepam is less desirable than midazolam when administrated as IM or IN.¹² It is important to note that benzodiazepine doses can be repeated every two to four minutes as needed, but when multiple doses of a benzodiazepine are used, respiratory depression should be anticipated, and it is important to have proper pediatric airway equipment available to use. For this reason, after two doses of benzodiazepine administered in the ED (in addition to dose administered by the pre-hospital personnel or paramedics), if seizure has not stopped, a second-line agent should be used.¹²

Second-line agents: The goal of seizure management with first line agent is to stop seizure within 10 minutes. If seizure still persists beyond this time, a second line agent should be used. In children, the following second line agents have similar efficacy and can be used interchangeably:¹³

• Fosphenytoin 20 mg/kg
• Valproic acid 40 mg/kg
• Levetiracetam 60mg/kg

A recent study suggested that levetiracetam may provide better hemodynamic outcome compared to fosphenytoin in certain situations.¹⁴ Second line agents do not work immediately, so they are considered adjunct therapy and not main stay of seizure therapy. They are, however, very effective in preventing seizure recurrence.¹⁵ 

While adult studies report cases of cardiac arrythmias and death from fosphenytoin due to its structural similarity to tricyclic antidepressants (blockade of fast acting sodium channels resulting in prolonged QRS duration and fatal wide complex ventricular tachyarrythmias), such reports in children are rare.¹⁶

Third-line agents: A variety of medications are considered as third-line agents. They are used for refractory seizures (lasting longer than 30 minutes). The majority of these agents require airway protection. Phenobarbital can be given without airway protection at the lower dose (5 mg/kg), but higher doses (10–20mg/kg) should be given only after the patient has their airway protected.¹⁷ Third-line agents include:¹⁷

• Phenobarbitol 5–20 mg/kg
• Propofol 1–5 mg/kg
• Pentobarbitol 5–20 mg/kg
• Ketamine 1–1.5 mg/kg
• Ketofol (ketamine 1 mg/kg with propofol 0.5 mg/kg)
• Lacosamide 6–10 mg/kg
• Topiramate (limited data on efficacy)

Burst suppression: If seizures require third-line agents, a burst suppression of 24–48 hours with a continuous infusion of pentobarbitol, midazolam, or propofol will be utilized and the patient will be placed on continuous EEG monitoring.^{18, 19}

Special considerations—neonates: First-line agent is midazolam 0.15 mg/kg, after which there is controversy. Phenobarbital 20 mg/kg (50 percent effective) has traditionally been use but other agents may be equally effective (fosphenytoin 20 mg/kg, lidocaine 2mg/kg, or leviteracetam 50 mg/kg).^20–23

Dr. Saidinejad is professor of clinical emergency medicine & pediatrics at the David Geffen School of Medicine at UCLA.

References

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