Pediatric Status Epilepticus Treatment & Management

Updated: Oct 06, 2014
  • Author: Rajesh Ramachandrannair, MBBS, MD, FRCPC; Chief Editor: Timothy E Corden, MD  more...
  • Print
Treatment

Approach Considerations

Status epilepticus (SE) treatment should follow a logical sequence of interventions. Every institution dealing with this problem should design a plan, such as the one outlined below, that is based on current information derived from authoritative sources, as well as on recent reviews of the literature, and the protocol should be communicated to the medical staff. Review the protocol at least annually.

The lack of a structured protocol has been blamed for increased morbidity from SE. [16] Litigation involving patients suffering sequelae of SE is often based on perceptions that treatment deviated from established standards of practice.

Physicians should become familiar with the pharmacology of the drugs used to treat SE. Prudence calls for doses of these drugs to be placed in visible locations within emergency departments (EDs), pediatric units, and nursing stations.

Treatment for generalized SE should be part of a continuum of the management for seizures of shorter duration. Any algorithm for treating seizures should consider the time of onset of the ictal activity (continuous or intermittent without recovery of consciousness) and the number and type of drugs that did not control the seizures, despite appropriate dosages and routes of administration. Remember that seizures of longer duration tend to be more difficult to treat.

Next:

Prehospital Care

Supportive care, including management of airway, breathing, and circulation (the ABCs), must be addressed in the prehospital setting. Emergency medical system (EMS) personnel should proceed as follows:

  • Secure the airway

  • Administer supplemental 100% oxygen

  • Infuse isotonic intravenous fluids and dextrose

  • Immobilize the cervical spine in patients with possible trauma

If the seizure fails to stop within 4-5 minutes or if the patient is continuing to seize at the time of EMS arrival, prompt administration of anticonvulsants may be indicated, if permitted by local protocols. Consider rectally administered diazepam (0.5 mg/kg/dose) or intramuscularly administered midazolam (0.1-0.2 mg/kg/dose; not to exceed a cumulative dose of 10 mg). [17]

If persons who know the patient, or who witnessed the onset of the seizures, are present at the scene, EMS providers may be able to collect information that offers clues to the cause of the SE.

Previous
Next:

Patient Stabilization

As in any medical emergency, attend to the ABCs first, before starting any pharmacologic intervention. Place patients in the lateral decubitus position to avoid aspiration of emesis and to prevent epiglottis closure over the glottis. Further adjustments of the head and neck may be necessary to improve patency of the airways (use care in the setting of potential neck trauma without full radiographic evaluation). Immobilize the cervical spine if trauma is suspected.

Administer 100% oxygen by facemask. Assist ventilation and use artificial airways (eg, endotracheal intubation) as needed. Suction secretions and decompress the stomach with a nasogastric tube.

Respiratory depression is a common complication of the management of prolonged seizures. Ensure that equipment is available to deliver supplemental oxygen and positive pressure ventilation when initiating anticonvulsant therapy.

Carefully monitor the patient's vital signs, including blood pressure. Carefully monitor the patient's temperature because hyperthermia may worsen brain damage caused by seizures.

In the first 5 minutes of seizure activity, before starting any medications, try to establish intravenous (IV) access and to obtain samples for laboratory tests and for seizure medication levels (see Workup). Infuse isotonic intravenous fluids plus glucose at a rate of 20 mL/kg/h (eg, 200 mL dextrose 5% in normal saline [D5NS] over 1 h for a 10-kg child).

In children younger than 6 years, use intraosseous (IO) infusion if intravenous access cannot be established within 5-10 minutes . Most available anticonvulsants may be administered intravenously or intraosseously.

If serum glucose is low or cannot be measured, give children 2 mL/kg of 25% glucose. Adults should receive 50 mL of 50% glucose, along with 100 mg of thiamine to avoid Wernicke- Korsakoff syndrome.

Other specific treatments may be indicated if the clinical evaluation identifies precipitants of the seizures. Selected agents and indications are as follows:

  • Naloxone - 0.1 mg/kg/dose intravenously preferably (if needed may administer intramuscularly/subcutaneously) for narcotic overdose

  • Pyridoxine - 50-100 mg intravenously/intramuscularly for possible dependency, deficiency, or isoniazid toxicity

  • Antibiotics - If meningitis is strongly suspected, initiate treatment with antibiotics prior to cerebrospinal fluid (CSF) analysis or CNS imaging

If the onset of the seizure was witnessed, initiate anticonvulsant treatment only after 5 minutes of seizure duration. Most seizures stop without intervention.

Obtain a history of the prehospital treatment of the seizures. Cumulative doses of benzodiazepine medication (prehospital included) increase the risk of respiratory failure.

In cases of repetitive convulsions without recovery of consciousness, the duration of the seizure is defined as the time elapsed from the onset of the first seizure to the termination of the last.

Call for the pediatric intensive care unit (PICU) service and respiratory therapists (or anesthesiologists) if seizures persist for more than 20 minutes.

The Table below is based on the Emergency Management Guidelines of Children's Hospital and Regional Medical Center. Step 1, which encompasses the first 0-5 minutes of care and thus precedes the actions outlined in this table, consists of addressing the patient's ABCs.

Table 1. Medical Treatment of Seizures and Status Epilepticus Based on Time Elapsed Since Seizure Onset (Steps 2-4) (Open Table in a new window)

Step

Medication

Dose

Alternatives

Step 2 (6-15 min)

Diazepam (Valium)

5-20 mg IV slowly; not to exceed infusion rate of 2 mg/min; pediatric dose is 0.3 mg/kg

If IV line is unavailable, use rectally administered (PR) diazepam at 0.5 mg/kg (not to exceed 10 mg) or midazolam (Versed) at 0.2 mg/kg intramuscularly (IM)*, IV, or intranasally*

Lorazepam* (Ativan)

2-4 mg IV slowly*; not to exceed infusion rate of 2 mg/min or 0.05 mg/kg over 2-5 min; pediatric dose is 0.05-0.1 mg/kg

Step 3 (16-35 min)

Phenytoin (Dilantin) or fosphenytoin (Cerebyx)†

20 mg/kg IV over 20 min; not to exceed infusion rate of 1 mg/kg/min; do not dilute in 5% dextrose in water (D5W)

If seizures persist, administer 5 mg/kg for 2 doses (if blood pressure is within the reference range and no history of cardiac disease is present)

If unsuccessful, administer phenobarbital 10-20 mg/kg IV (not to exceed 700 mg IV); increase infusion rate by 100 mg/min; phenobarbital may be used in infants before phenytoin; be prepared to intubate patient; closely monitor hemodynamics and support blood pressure as indicated

Step 4 (45-60 min)‡

Pentobarbital anesthesia (patient already intubated)

Loading dose: 5-7 mg/kg IV; may repeat 1-mg/kg to 5-mg/kg boluses until EEG exhibits burst suppression; closely monitor hemodynamics and support blood pressure as indicated

Maintenance dose: 0.5-3 mg/kg/h IV; monitor EEG to keep burst suppression pattern at 2-8 bursts/min

Midazolam* infusion loading dose: 100-300 mcg/kg IV followed by IV infusion of 1-2 mcg/kg/min; increase by 1-2 mcg/kg/min every 15 min if seizures persist (effective range 1-24 mcg/kg/min); closely monitor hemodynamics and support blood pressure as indicated; when seizures stop, continue same dose for 48 h then wean by decrements of 1-2 mcg/kg/min every 15 min

Propofol* initial bolus: 2 mg/kg IV; repeat if seizures continue and follow by IV infusion of 5-10 mg/kg/h, if necessary, guided by EEG monitoring; taper dose 12 h after seizure activity stops; closely monitor hemodynamics and support blood pressure as indicated

With phenobarbital-induced anesthesia, repeated boluses of 10 mg/kg are administered until cessation of ictal activity or appearance of hypotension; closely monitor hemodynamics and support blood pressure as indicated

*Not approved by the FDA for the indicated use.

†Doses for fosphenytoin administered in phenytoin equivalents (PE).

‡An alternative third step preferred by some authors is midazolam

administered by continuous IV infusion with a loading dose 0.1-0.3 mg/kg followed by infusion at a rate of 0.1-0.3 mg/kg/h.

Previous
Next:

Anticonvulsant Selection

The optimal protocol for management of SE begins with a benzodiazepine, either lorazepam or diazepam. [18] In the United States, lorazepam is the drug of choice in patients with intravenous or intraosseous access. Lorazepam (0.05-0.1 mg/kg IV or IO slowly infused over 2-5 min) has rapid onset and long duration of anticonvulsant action. It is preferred over diazepam, [19, 20] although one review found lorazepam and diazepam equally effective for controlling SE in children. [21, 22]

If an IV line cannot be established rapidly in a child who is too old for IO infusion, use per rectum (PR) diazepam. Midazolam (0.1-0.2 mg/kg IM) is the most effective choice when IV or IO access is not immediately available, but IM midazolam is not approved by the US Food and Drug Administration (FDA) for that indication.

Midazolam is the only benzodiazepine that can be administered safely intramuscularly while providing rapid onset equivalent to that of intravenous agents and a moderate duration of action. Intranasal midazolam may also be an option in children with prolonged seizure without an IV access.

In one study, no difference in efficacy was observed between caregiver-administered intranasal midazolam and rectal diazepam for terminating sustained seizures (ie, >5 minutes) in children at home. Caregiver's satisfaction was higher with the inhaled midazolam (easier to administer) and the median time from medication administration to seizure cessation was 1.3 minutes less for inhaled midazolam compared with rectal diazepam. [23]

If the seizures cease, no further drugs are immediately necessary. The etiology of SE epilepticus should then be investigated.

If benzodiazepine therapy proves ineffective, IV or IO fosphenytoin or phenytoin is used. These agents are effective for most idiopathic generalized seizures and for posttraumatic, focal, or psychomotor SE. Fosphenytoin offers the advantage of a potentially rapid rate of administration with less risk of venous irritation and vascular compromise of the infused limb (eg, purple-glove syndrome).

The loading dose of phenytoin is 20 mg/kg IV or IO; for fosphenytoin, it is 20 mg/kg PE IV or IO. A full loading dose should be delivered unless the patient is known to have a current therapeutic level. With phenytoin, use a slow rate of infusion (< 1 mg/kg/min or < 50 mg/min) to avoid hypotension or cardiac arrhythmias. Although respiratory depression that requires endotracheal intubation may occur at any time during treatment of GTCSE, it is especially common during administration of phenytoin/fosphenytoin.

If fosphenytoin or phenytoin is not effective, phenobarbital (20 mg/kg IV/IO) is the third-line therapy. In many pediatric institutions, phenobarbital is the second-line choice, rather than fosphenytoin or phenytoin, especially for febrile and neonatal SE. Phenobarbital's major disadvantages are that it significantly depresses mental status and causes respiratory difficulty. Obtain serum anticonvulsant levels prior to administering additional long-acting anticonvulsants such as phenytoin or fosphenytoin.

For more information, see the Medscape Reference article Antiepileptic Drugs.

Refractory status epilepticus

The term refractory GTCSE has been used when seizures do not respond to benzodiazepines, phenytoin/fosphenytoin, and phenobarbital. Several options are presently available for these patients.

Barbiturate anesthesia is among the most popular treatments, although midazolam infusions (neither is approved by the FDA) have gained growing acceptance in the United States over the past 5 years. In the United States, barbiturate anesthesia is commonly performed with pentobarbital infusions. Pentobarbital is given in a loading dose of 5-10 mg/kg IV or IO, followed by 0.5-3 mg/kg/hr. In the United Kingdom, thiopental (thiopentone) is often used rather than pentobarbital. High-dose phenobarbital has been used in patients with GTCSE. All barbiturates used in anesthetic doses have been associated with such complications as hypotension, cardiac depression, and infections.

Midazolam and propofol are gaining increasing acceptance throughout the world as alternative treatments for refractory GTCSE, thanks to the comparative ease of handling these drugs in a continuous infusion. [24] However, propofol is not currently recommended for long-term control of SE, due to reports of severe acidosis and movement disorder after prolonged use. Also worrisome is the association of propofol-related metabolic acidosis in patients on the ketogenic diet.

Midazolam has been used, even in neonates, and has a reasonably predictable pharmacology, although movement disorders have been reported from prolonged use of midazolam for sedation. [25] Midazolam is given in a loading dose of 0.2 mg/kg IV or IO, followed by 0.75-10 mcg/kg/min.

In a few cases, adding a maintenance anticonvulsant medication to the patient’s regimen may help wean the patient off a continuous barbiturate infusion. Although the experience is still very limited, both IV valproic acid and topiramate via nasogastric tube have been used with that goal.

High-dose topiramate has been used in adults with SE, at doses as high as 1600 mg/day. [26] One pediatric study used relatively lower initial doses of 2-3 mg/kg/day before proceeding within 48-72 hours to a maintenance dose of 5-6 mg/kg/day (in 2 divided doses daily), which terminated the episode of SE. [27] Another study reported a loading dose of 10 mg/kg followed by 5 mg/kg/day maintenance (in 2 divided doses daily). [28] Treatment of SE with topiramate is suggested by the neuroprotective action of this drug in animal models. Nonetheless, further data are necessary to show similar action in humans.

Intravenous valproic acid is used for 3-Hz spike and wave stupor (absence SE) and myoclonic SE in cases of juvenile myoclonic epilepsy and postanoxic myoclonus. [29, 30] Treatment of convulsive status (ie, GTCSE) with IV valproic acid after failure of other drugs (eg, benzodiazepines, phenytoin, phenobarbital) has been rarely reported. Both secondary and primary GTCSE seem to equally respond to IV valproic acid.

A loading dose of 15-20 mg/kg is used, followed by 10 mg/kg every 6 hours. Alternatively, Uberall et al recommend a loading dose of 20-40 mg/kg over 5 minutes, followed by an infusion at a rate of 5 mg/kg/h. [31] After 12 hours of clinical and EEG cessation of seizures, the dose is reduced to 1 mg/kg every 2 hours.

Reports have shown the efficacy of levetiracetam as an add-on therapy in adults with refractory SE, with reported loading doses of 500-3000 mg/day and a maintenance dose of 2000-3000 mg/d. In children, the reported loading dose is 30-40 mg/kg. [32, 33, 34]

In Europe, alternative agents such as paraldehyde, lidocaine (Sweden and United Kingdom), and chlormethiazole (mostly United Kingdom) have been used. Paraldehyde is no longer commercially available in the United States, whereas chlormethiazole is not approved by the FDA. Lidocaine is unpopular in the United States because of its narrow therapeutic index and proconvulsant effect at toxic levels.

Paraldehyde is a very effective drug, despite problems (eg, sterile abscess, pulmonary edema), but was discontinued from the US market in 2008. Respiratory failure and hypotension of sudden onset has been described. Shorvon recommends pediatric doses of 0.07-0.35 mL/kg. [35] The adult dose is 5 mL PR diluted on the same volume of water.

Exposure to air and light causes conversion of paraldehyde to acetaldehyde and then to acetic acid, with subsequent metabolic acidosis when administrated. Paraldehyde dissolves some plastic syringes and tubing if not used immediately.

Approximately 80% of the paraldehyde is absorbed after a single rectal dose. Because of the high solubility of paraldehyde in lipids, the passage through the blood brain barrier may depend more on the cerebral blood flow; this is an attractive quality because of the possibility of a differential absorption concentration of the drug by the regions of the cortex involved in the epileptiform activity because they have higher blood flow than the rest of the brain during seizures.

A therapeutic trial with folinic acid (0.5-1 mg/kg) and enteral pyridoxine (up to 30 mg/kg/day) for a week is worth considering in prolonged refractory status epilepticus.

Previous
Next:

Further Inpatient Care

Most children with an episode of SE should be admitted for inpatient observation, evaluation, and treatment. Any child with persistent altered mental status (despite cessation of seizure activity) or with prolonged status epilepticus should be admitted to a pediatric critical care unit.

Treat patients with status epilepticus (SE) who have suspected herpes encephalitis with acyclovir until the diagnosis can be confirmed. Suspect herpes virus encephalitis in all patients with fever, mental status changes, and de novo onset of partial seizures, with or without secondary generalization.

Treatment of catscratch disease is not universally efficacious. Rifampin, ciprofloxacin, and trimethoprim-sulfamethoxazole have been successfully used.

Electrolyte disturbances may cause or perpetuate seizures; hypocalcemia and hyponatremia are the most common. Efforts to correct hyponatremia should be performed carefully because quick shifts in serum osmolality may cause irreversible brain damage from central pontine myelinolysis. Correction of hypocalcemia with IV calcium gluconate should be performed under electrocardiographic (ECG) monitoring because of the possibility of cardiac arrhythmias.

Previous
Next:

Long-Term Antiepileptic Therapy

Although a complete guide for outpatient management of epilepsy is beyond the scope of this article, the Epilepsy Foundation Working Group on Status Epilepticus recommends starting some patients, including those with a history of epilepsy or brain lesion, on long-term antiepileptic therapy after an episode of SE.

No long-term therapy is indicated for SE caused by transient problems (eg, metabolic disturbances such as hyponatremia, intoxications). No consensus has been reached regarding the need for treatment after an instance of febrile SE or when a first unprovoked seizure is an SE episode.

Although many studies have shown that recurrent seizure risk is unrelated to seizure duration, a recurring GTCSE episode is more likely to be a prolonged seizure.

Knowledge of the seizure type and EEG pattern can help confirm the diagnosis of an epileptic syndrome and guide the selection of anticonvulsant medication. Patients with partial seizures respond better overall to carbamazepine, phenytoin, and phenobarbital (infants).

Valproic acid and phenobarbital are better treatments for patients with generalized tonic-clonic seizures, although carbamazepine and phenytoin can also be administered for patients with secondary generalized seizures. Valproic acid carries a higher risk of liver failure in patients younger than 2 years and those on polypharmacy.

Previous
Next:

Consultations

After initial emergency stabilization, consider consultation with the following specialists:

  • Pediatric emergency or critical care specialist or general pediatrician

  • Pediatric neurologist

  • Pediatric neurosurgeon if needed

Transfer is prudent unless the hospital facility has a pediatric critical care unit and staff familiar with the risks and complications of SE in children.

A child who has a single generalized tonic-clonic seizure for the first time often does not receive long-term anticonvulsant therapy. Consult a pediatric neurologist.

Previous