Pediatric Status Epilepticus Follow-up

Author: Grace M Young, MD; Chief Editor: Richard G Bachur, MD

MEDSCAPE

Background
Status epilepticus is defined as recurrent or continuous seizure activity lasting longer than 30 minutes in which the patient does not regain baseline mental status.[1]

Pathophysiology
Seizures result from rapid abnormal electrical discharges from cerebral neurons. This presents clinically as involuntary alterations of consciousness or motor activity. Consumption of oxygen, glucose, and energy substrates (eg, ATP, phosphocreatine) is significantly increased in cerebral tissue during seizures. Optimal delivery of these metabolic substrates to cerebral tissue requires adequate cardiac output and intravascular fluid volume. Prolonged seizures are associated with cerebral hypoxia, hypoglycemia, and hypercarbia and with concurrent and progressive lactic and respiratory acidosis. When cerebral metabolic needs exceed available oxygen, glucose, and metabolic substrates (especially during status epilepticus), neuronal destruction can occur and may be irreversible. Hypoxia, hypercarbia, hyperthermia, tachycardia, hypertension, hyperglycemia, hyperkalemia, and lactic acidosis result from massive sympathetic discharge.

Epidemiology
Frequency United States

Seventy percent of children younger than 1 year who are subsequently diagnosed with epilepsy present with status epilepticus as the initial symptom of their illness. In children with epilepsy, 20% have status epilepticus within 5 years of diagnosis. Five percent of children with febrile seizures present with status epilepticus.
International

Rates are similar to those in the United States.

Mortality/Morbidity

In the United States, the overall mortality is 10-15%.

Sex

No sexual predilection is recognized.

Age

Status epilepticus is common at any age. Certain etiologies are more prevalent in selected age groups (see Causes).

History
In the initial presentation of status epilepticus, a directed history suffices. Obtain a more detailed history after stabilization, including the following details: The course of current seizure activity - Time and nature of onset of seizure activity; involvement of extremities or other body parts; nature of movements (eg, eye movements, flexion, extension, stiffening of extremities), including any focal movements and details of postictal neurologic deficit; incontinence; cyanosis (perioral or facial); duration of seizure activity prior to medical attention; mental status after cessation of seizure activity Fever or intercurrent illnesses

Prior history of seizures - If present, specify medications, anticonvulsant use, and compliance. Head injury (recent and remote) Central nervous system (CNS) infection or disease (eg, meningitis, neurocutaneous syndrome) Intoxication or toxic exposure (see Causes for examples) Other CNS abnormality (eg, ventricular-peritoneal shunt, prior CNS trauma) Birth history and developmental delay (eg, anoxic encephalopathy, cerebral palsy) Other medical history (eg, acquired immunodeficiency syndrome, systemic lupus erythematosus, type 1 diabetes mellitus)

Physical
Perform a rapid, directed physical and neurologic examination during status epilepticus, followed by a detailed examination when the child is stabilized. Signs of sepsis or meningitis include the following: Temperature more than 38.5C; in patients younger than 2-3 months, more than 38.0C Respiratory distress Cyanosis Poor peripheral perfusion Bulging fontanelles in infant Meningismus (in children >12-18 mo) Presence of petechiae or purpura, herpetic vesicles Evidence of head or other CNS injury includes the following: Bradycardia, tachypnea, and hypertension (Cushing triad for signs of increased intracranial pressure) Poor pupillary response Asymmetry on neurologic examination Abnormal posturing Gross deformity or soft tissue injury to head Hallmarks of neurocutaneous syndromes (eg, port wine stain) may be noted.

Causes
Neonates (first month of life) Birth injury (eg, anoxia, hemorrhage) and congenital abnormalities Metabolic disorders (eg, hypoglycemia, hypocalcemia, hyponatremia) and inborn errors of metabolism (eg, lipidoses, amino acidurias) Infection (eg, meningitis) Early childhood (< 6 y) Birth injury Febrile convulsions (3 mo to 6 y) Infection Metabolic disorders Trauma Neurocutaneous syndromes Cerebral degenerative diseases Tumors Idiopathic Children and adolescents (>6 y) Birth injury

Trauma Infection Epilepsy with inadequate drug levels Cerebral degenerative disease Tumor Toxins Idiopathic Toxins and medications Topical anesthetics (eg, lidocaine) Anticonvulsant overdose Camphor Hypoglycemic agents (eg, insulin, ethanol) Carbon monoxide Cyanide Heavy metals (eg, lead) Pesticides (eg, organophosphate) Cocaine Phencyclidine Belladonna alkaloids Nicotine Sympathomimetics (eg, amphetamines, phenylpropanolamine [recalled from US market]) Tricyclic antidepressants

Differential Diagnoses

Herpes Simplex Herpes Simplex Encephalitis Neoplasms, Brain Pediatrics, Bacteremia and Sepsis Pediatrics, Febrile Seizures Pediatrics, Meningitis and Encephalitis Toxicity, Amphetamine Toxicity, Anticholinergic Toxicity, Antidepressant Toxicity, Carbon Monoxide Toxicity, Cocaine Toxicity, Cyanide Toxicity, Cyclic Antidepressants Toxicity, Heavy Metals Toxicity, Lead Toxicity, Local Anesthetics Toxicity, Medication-Induced Dystonic Reactions Toxicity, Methamphetamine Toxicity, Organophosphate and Carbamate

Toxicity, Phencyclidine Toxicity, Sympathomimetic

Laboratory Studies
Obtain laboratory studies based on age and likely etiologies. Blood glucose level using immediate bedside testing (eg, Dextrostix), particularly if the child or other household members are dependent on insulin or other hypoglycemic agents Electrolyte levels Calcium and magnesium levels, particularly in neonates ABG levels Toxicology screen Anticonvulsant levels (if indicated by history of ingestion or existent therapy) WBC count: An elevated WBC count may be due to demargination, returning to reference ranges over 12-24 hours. Carboxyhemoglobin levels

Imaging Studies
Stabilize all children before CT scanning or other imaging studies are performed. Obtain imaging studies based on likely etiologies. Cervical spine radiographs, if potential trauma is suspected. A head CT scan is the best diagnostic imaging study, particularly if the following are suspected:

Hemorrhage Midline shift Mass lesion

MRI is not a diagnostic tool, unless it is immediately available and the child's cardiorespiratory status is stable.

Other Tests
Electroencephalography For unremitting status epilepticus Usually performed in a critical care setting

Procedures
Lumbar puncture with opening pressure

For prolonged status epilepticus of unknown etiology For immunocompromised patients

Prehospital Care

Secure the airway. Administer supplemental 100% oxygen. Infuse isotonic intravenous fluids and glucose. Immobilize the cervical spine in patients with possible trauma.

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).[2]

Emergency Department Care

The principles of treatment are to terminate the seizure while resuscitating the patient, treating complications, and preventing recurrence. Assessment and stabilization of ABCs concurrent with management of the seizure is imperative. 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. Immobilize the cervical spine if trauma is suspected. Closely monitor vital signs, cardiorespiratory function, and oxygen saturation. Perform rapid blood glucose assay (eg, Dextrostix) at bedside. Establish intravenous access. Use intraosseous (IO) infusion if intravenous access is not immediately available in the child younger than 6 years. Most available anticonvulsants may be administered intravenously or intraosseously. Infuse isotonic intravenous fluids 20 mL/kg with glucose (eg, 200 mL dextrose 5% in normal saline [D5NS] intravenously over 1 h for a 10-kg child). Consider treatment with the following agents:

Dextrose - 0.25-0.5 g/kg/dose (1-2 mL of 25% dextrose) intravenously for hypoglycemia; not to exceed 25 g/dose Naloxone - 0.1 mg/kg/dose intravenously preferably (if needed may administer intramuscularly/subcutaneously) for narcotic overdose Thiamine - 100 mg intramuscularly for possible deficiency Pyridoxine - 50-100 mg intravenously/intramuscularly for possible deficiency Antibiotics - If meningitis is strongly suspected, initiate treatment with antibiotics prior to cerebrospinal fluid (CSF) analysis or CNS imaging.

Administer anticonvulsant medication. The optimal protocol for management of status epilepticus begins with a benzodiazepine. In the United States, lorazepam is the first drug of choice in patients with intravenous or intraosseous access. For patients without parenteral access, intramuscular midazolam is best. If the seizures cease, no further drugs are immediately necessary, and the etiology of status epilepticus should be investigated. If seizures continue, administer intravenous phenytoin or parenteral fosphenytoin. If these are not effective, administer intravenous phenobarbital titrated to induce barbiturate coma. Finally, consider general anesthesia with pentobarbital or midazolam. The goal is prompt cessation of seizure activity. Patiently allow infused anticonvulsants to act before using additional anticonvulsants. Proceed to the next drug if seizure activity continues. Lorazepam (0.05-0.1 mg/kg intravenously/IO slowly infused over 2-5 min) has rapid onset and long duration of anticonvulsant action. It is preferred over diazepam. Phenytoin (18-20 mg/kg intravenously/IO) or fosphenytoin (15-20 mg/kg intravenously/IO) loading doses: These long-acting anticonvulsants usually are infused if benzodiazepines do not stop the seizures. Phenytoin and fosphenytoin are effective for most idiopathic generalized seizures and for posttraumatic, focal, or psychomotor status epilepticus. Use a slow rate of infusion (< 1 mg/kg/min or < 50 mg/min) to avoid hypotension or cardiac arrhythmias. A full loading dose should be delivered unless the patient is known to have a current therapeutic level.

Midazolam (0.1-0.2 mg/kg intramuscularly) is most effective when intravenous or intraosseous access is not immediately available.[3] Midazolam is the only benzodiazepine that can be administered safely intramuscularly with equivalent rapid onset and moderate duration of action. Phenobarbital (20-25 mg/kg intravenously/IO) is effective for febrile and neonatal status epilepticus and may be infused after lorazepam or other benzodiazepines if the child is likely to have these types of seizures. 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.
General anesthesia

Pentobarbital (5-10 mg/kg intravenously/IO loading dose followed by 0.5-3 mg/kg/h) or midazolam (0.2 mg/kg intravenously/IO loading dose followed by 0.75-10 mcg/kg/min) All children must be intubated and paralyzed, have continuous cardiorespiratory and EEG monitoring, and be in a pediatric critical care setting.

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

Medication Summary
Benzodiazepines, hydantoins, and barbiturates have anticonvulsant properties. Choose a parenteral preparation with rapid onset and long duration of action with the least amount of sedation and respiratory depression. Titrate for clinical response by waiting an adequate length of time for attainment of therapeutic levels in the brain.

Benzodiazepines
Class Summary

By increasing the action of GABA, which is a major inhibitory neurotransmitter in the brain, may depress all levels of CNS, including limbic and reticular formation. 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.[4]
Lorazepam (Ativan)

Sedative hypnotic with short onset of effects and relatively long half-life. Preferred over diazepam because of significantly longer duration of action and equivalent rapid onset of action. Important to monitor patient's blood pressure after administering dose. Adjust prn.

Diazepam (Valium) For treatment of seizures. Depresses all levels of CNS (eg, limbic and reticular formation), possibly by increasing GABA activity. Effective for prehospital use as PR administration. Has a long half-life but rapidly redistributes from the CNS. Requires administration of the longer-acting phenytoin or phenobarbital because of very short duration of seizure control.

Do not administer >1-2 mg/min IVP in children or > 5 mg/min in adults.

Midazolam (Versed) Used as alternative in termination of refractory status epilepticus. Because midazolam is water soluble, takes approximately 3 times longer than diazepam to peak EEG effects. Thus, clinician must wait 2-3 min to fully evaluate sedative effects before initiating procedure or repeating dose. DOC for child without immediate IV or IO access (available IM).

Barbiturates
Class Summary

These agents suppress CNS from reticular activating system (presynaptic and postsynaptic).
Phenobarbital (Barbita, Luminal) Effective for febrile and neonatal status epilepticus. Can be administered PO. In status epilepticus, it is important to achieve therapeutic levels as quickly as possible. IV dose may require approximately 15 min to attain peak levels in the brain. If injected continuously until convulsions stop, brain concentrations may continue to rise and can exceed that required to control seizures resulting in subsequent toxicity. Important to use minimal amount required and wait for anticonvulsant effect to develop before administering a second dose.

If IM route chosen, administer into areas with little risk of encountering a nerve trunk or major artery such as one of the large muscles (eg, gluteus maximus, vastus lateralis). A permanent neurologic deficit may result from injecting into or near peripheral nerves. Restrict IV use to conditions in which other routes are not possible, either because patient is unconscious or because prompt action is required. IV administration should be < 50 mg/min. Parental product contains 68% propylene glycol. Ensure monitoring for hypotension, bradycardia, and arrhythmias upon administration.

Hydantoins
Class Summary

These agents stabilize neuronal membranes and decrease seizure activity.

Fosphenytoin (Cerebyx) Diphosphate ester salt of phenytoin that acts as water-soluble prodrug of phenytoin. Following administration, plasma esterases convert fosphenytoin to phosphate, formaldehyde, and phenytoin.

To avoid need to perform molecular weight-based adjustments when converting between fosphenytoin and phenytoin sodium doses, express dose as phenytoin sodium equivalents (PE). Although can be administered IV and IM; IV route is route of choice and should be used in emergency situations.

Concomitant administration of an IV benzodiazepine usually is necessary to control status epilepticus. Full antiepileptic effect, whether administered as fosphenytoin or parenteral phenytoin, is not immediate. Not currently recommended for acute control of status epilepticus because of its slow onset of action. Prepare drug in 100 mL of NS or D5W.
Phenytoin (Dilantin) May act in motor cortex where may inhibit spread of seizure activity. Activity of brain stem centers responsible for tonic phase of grand mal seizures also may be inhibited. Effective for idiopathic, posttraumatic, focal, and psychomotor status epilepticus. Individualize doses. Administer larger dose before retiring if dose cannot be divided equally.

Administer only in saline solutions (incompatible when mixed with dextrose-containing solutions).

General anesthetics
Class Summary

All children must be intubated and paralyzed and must have continuous cardiorespiratory and EEG monitoring in a pediatric critical care unit. Pentobarbital may be required when seizures persist despite appropriate administration of other antiseizure agents.
Pentobarbital (Nembutal) Short-acting barbiturate with sedative, hypnotic, and anticonvulsant properties. Can produce all levels of CNS mood alteration. Acts primarily on cerebral cortex and reticular formation through decreased neuronal synaptic activity.

Further Inpatient Care

Most children with an episode of status epilepticus 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.

Inpatient & Outpatient Medications

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.

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

Deterrence/Prevention
Patients should avoid exposure to specific causes.

Complications
Complications of status epilepticus may include the following:

Anoxic brain damage Aspiration Head trauma Minor soft tissue trauma Joint dislocation: Posterior shoulder dislocation is a classic complication and is difficult to diagnose in the unconscious patient. Complications as a result of the underlying cause

Prognosis
Outcome depends on the underlying cause.

Patient Education
Patients should follow instructions from the pediatric neurologist. Patients should maintain compliance with anticonvulsant therapy. For excellent patient education resources, visit eMedicine's Brain and Nervous System Center. Also, see eMedicine's patient education article Epilepsy.

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