Children may have been treated at home or by EMS personnel. Take this into consideration when treating refractory status epilepticus.
Benzodiazepines (Table 131-4) are the first-line treatment for prolonged seizures because of their rapid onset and effectiveness; however, not all benzodiazepines or routes are available in the prehospital setting, and establishing IV access can be difficult in a child who is having a seizure.7,10,15 Benzodiazepines may be given by the intranasal, buccal, rectal, or intraosseous route when an IV is difficult to place.11,16–25
Table 131-4 Benzodiazepines for Initial Treatment of Prolonged Seizures |Favorite Table|Download (.pdf)
Table 131-4 Benzodiazepines for Initial Treatment of Prolonged Seizures
Onset of Action
Duration of Action
IV, IO, IN
Rectal diazepam is one “rescue” medication commonly used at home and by EMS personnel. The advantage is that no refrigeration or IV line is needed. The disadvantage is its short half-life and the need for rectal administration. Midazolam, also an effective rescue medication, can be given safely via the intranasal route using a mucosal atomization device (MAD®, Wolfe Tory Medical, Inc., Salt Lake City, UT).20,21,26 Midazolam can also be given buccally.1,12,14–24 Lorazepam is not generally used in the prehospital setting because of its need for refrigeration and recommendations that it only be administered through an IV line. There is new evidence that intranasal lorazepam using a MAD® may be as effective as IV lorazepam in the treatment of status epilepticus.25,27
Most seizures stop within 5 minutes and do not require medical treatment.10 Status epilepticus is a medical emergency, however, and is more responsive to medications when treated early, and treatment becomes less effective with time.11,17,28 An overview of one treatment algorithm for status epilepticus is depicted in Figure 131-3.
Initial treatment of status epilepticus: an example of one approach. IN = intranasal; PE = phenytoin sodium equivalents.
Administer oxygen by facemask and institute continuous pulse oximetry and cardiac monitoring. Establish IV or intraosseus (IO) access, but administer medication early via alternate routes (intranasal, IM, PR, buccal) if there is delay.6 Obtain bedside glucose testing and electrolyte levels when available.4,7,11 Consider additional laboratory studies and imaging as directed by the history and examination. Subtherapeutic antiepileptic drug levels are found in almost one third of children with epilepsy presenting in status epilepticus.29 Consider central nervous system infection in the child with fever and status epilepticus.
The decision to intubate is clinical. Intubate for apnea and persistent hypoxia. Blood gas concentrations are not needed to guide the decision to intubate, because the seizure itself causes a metabolic and respiratory acidosis. The use of a paralytic with intubation obscures the ability to assess ongoing seizure activity, so arrange continuous electroencephalogram monitoring for intubated patients with status epilepticus.
Administer a benzodiazepine (Table 131-4) as the initial treatment for status epilepticus.11,16,17 Benzodiazepines are effective in terminating seizure activity and act by binding to gamma-aminobutyric-acid receptors7; they are preferred over other medications because of their rapid onset of action.11,16 Lorazepam is generally preferred over other benzodiazepines because of its longer duration of action and some evidence that it has fewer side effects (including respiratory depression) than the other benzodiazepines.30,31
Generally, if two doses of benzodiazepines are administered without effect, additional doses are unlikely to be successful and increase the risk for respiratory depression.32 Because there is no standard treatment for refractory status epilepticus, approaches to treatment and order of medication administration vary,11,33,34 and Figure 131-3 represents one approach to refractory status epilepticus.
If a seizure persists after two doses of a benzodiazepine have been given, fosphenytoin, levetiracetam, phenobarbital, or valproic acid are preferred second-line treatment choices.11,33,34 Currently, there are no randomized controlled trials that compare these four treatment options, but a number of small studies have shown the efficacy of each. A provider should generally choose two of the four medications for refractory status epilepticus and then move on to a fourth-line treatment option if a seizure persists. Table 131-5 summarizes the medications used for refractory status epilepticus.
Table 131-5 Medications for Refractory Status Epilepticus |Favorite Table|Download (.pdf)
Table 131-5 Medications for Refractory Status Epilepticus
20–30 milligrams/kg PE
5–10 milligrams/kg PE
30 milligrams/kg PE
3 milligrams/kg/min PE
Second- and Third-Line Treatments
Phenytoin and its prodrug, fosphenytoin, inhibit neuronal firing by stabilizing sodium channels and reducing neuronal calcium uptake. Fosphenytoin is safe and effective11,33,34; it can be administered more rapidly with fewer cardiac effects than phenytoin, which can precipitate in an IV line and cause significant tissue injury with extravasation.31 Fosphenytoin is preferred as second-line treatment over phenobarbital except in neonates, mainly because it has a different mechanism of action from benzodiazepines and phenobarbital, which both bind gamma-aminobutyric-acid receptors.11,31 Monitor serum levels in patients with renal or hepatic dysfunction.31
Levetiracetam is also safe and effective for treatment of status epilepticus, although it has not been prospectively compared with other anticonvulsants.11,33–42 Levetiracetam is eliminated solely via renal excretion and has no hepatic metabolism, and it has few adverse effects and essentially no drug and food interactions.11,33–43 Another advantage of levetiracetam over fosphenytoin (phenytoin) and phenobarbital is that it is commonly used for maintenance therapy for multiple seizure types.39
Phenobarbital is most commonly used in neonates who are often maintained on daily phenobarbital for subsequent seizure control.44 Side effects include sedation and cardiorespiratory depression, which may be amplified by benzodiazepines.4,11,33,34
Valproic acid is approved by the U.S. Food and Drug Administration for treatment of status epilepticus and is also effective for partial and generalized seizures.45 Consider valproic acid for treatment of children already taking this medication who are suspected of having subtherapeutic levels. Twenty to 40 milligrams/kg of IV valproic acid effectively terminates seizure activity with few side effects or less sedation.11,33,34,45–47 Use with caution in children at risk for metabolic disease, because in rare cases it may cause hepatic failure11,33,34 and has rarely been associated with thrombocytopenia.33
Propofol is an IV anesthetic agent that acts on gamma-aminobutyric-acid receptors differently from benzodiazepines or barbiturates34 and has been shown to effectively treat refractory status epilepticus better than pentobarbital.34,48,49 Propofol has a rapid onset of action, but it is quickly metabolized and should be followed by continuous infusion if seizure activity persists and must be infused slowly because of the potential for serious side effects, including bradycardia, apnea, and hypotension.34,48 Prepare for intubation and provide continuous cardiopulmonary when administering propofol for seizures.34,48,49 Patients receiving sustained propofol administration (>24 hours) should be monitored for development of “propofol infusion syndrome” (metabolic acidosis, rhabdomyolysis, renal failure, and cardiac failure).34,50
A “pentobarbital coma,” or continuous infusion, has been used for refractory status epilepticus not responsive to multiple anticonvulsant treatments with reported efficacy between 74% and 100%.34 Side effects include respiratory depression, hypotension, and decreased cardiac contractility, and most patients require intubation and inotropic support.34
Midazolam infusion has a low rate of adverse effects; however, compared with propofol and pentobarbital, midazolam has a higher rate of seizure recurrence.34
Treatment of Glucose and Electrolyte Abnormalities
Most laboratory results are not immediately available when treating status epilepticus. Abnormal glucose, sodium, calcium, and magnesium, especially low levels, can cause seizures. Seizures caused by abnormal electrolytes respond poorly to conventional medication but do respond to replacement electrolyte therapy.
Hypoglycemia can be the cause or an effect of prolonged seizures, and bedside testing is essential in seizing patients. Treat hypoglycemia with a rapid infusion of 2 mL/kg of 25% dextrose in water or 5 mL/kg of 10% dextrose in water.7
Hyponatremia (serum sodium <135 mEq/L) is most commonly seen in infants <6 months of age and sometimes in athletes and can cause seizures, especially if the serum sodium is <120 mEq/L. The goal of therapy is to correct the level to >120 mEq/L quickly and then correct to normal levels over the next 24 hours (see Chapter 143, Fluid and Electrolyte Therapy in Infants and Children). Treat the seizing patient with hyponatremia with 3% NaCl 4 to 6 mL/kg over 20 minutes, or begin an infusion of 20 mL/kg of 0.9% NaCl if 3% NaCl is not immediately available. The sodium level should be rechecked after the bolus to determine whether a second bolus is necessary.6
Hypocalcemia is more common in neonates and young infants and may be associated with congenital anomalies such as DiGeorge’s syndrome. Calcium gluconate 0.3 mL/kg over 5 to 10 minutes is preferred over calcium chloride when infusing through a small peripheral IV, as calcium chloride can cause local irritation.6
Treat hypomagnesemia (serum magnesium <1.5 mEq/L) with magnesium sulfate 50 milligrams/kg IV infused over 20 minutes.