You are in: eMedicine Specialties > Emergency Medicine > PEDIATRIC Pediatrics, Status EpilepticusArticle Last Updated: Jun 16, 2008AUTHOR AND EDITOR INFORMATIONSection 1 of 10
  Author: Grace M Young, MD, Associate Professor, Department of Pediatrics, University of Maryland Medical Center Grace M Young is a member of the following medical societies: American Academy of Pediatrics and American College of Emergency Physicians Editors: Garry Wilkes, MBBS, FACEM, Director of Emergency Medicine, Bunbury Health Service, Western Australia Country Health Service; Adjunct Associate Professor, School of Exercise, Biomedical and Health Sciences, Faculty of Computing, Health and Science, Edith Cowan University; Medical Director, St John Ambulance Service; Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine.com, Inc; Wayne Wolfram, MD, MPH, Clinical Associate Professor, Departments of Pediatrics, Children's Hospital and University of Cincinnati; John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center; Richard G Bachur, MD, Assistant Professor of Pediatrics, Harvard Medical School; Associate Chief and Fellowship Director, Attending Physician, Division of Emergency Medicine, Children's Hospital of Boston Author and Editor Disclosure Synonyms and related keywords: status epilepticus, SE, epilepsy, status epilepticus in children, seizure, febrile seizures, continuous seizure activity, hypoxia, hypercarbia, hyperthermia, tachycardia, hypertension, hyperglycemia, hyperkalemia, hypoglycemia, lactic acidosis, respiratory acidosis, epilepsy, sepsis, meningitis, respiratory distress, meningismus INTRODUCTIONSection 2 of 10
  BackgroundStatus 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 PathophysiologySeizures 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. FrequencyUnited StatesSeventy 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. InternationalRates are similar to those in the United States. Mortality/MorbidityIn the United States, the overall mortality is 10-15%. SexNo sexual predilection is recognized. AgeStatus epilepticus is common at any age. Certain etiologies are more prevalent in selected age groups (see Causes). CLINICALSection 3 of 10
HistoryIn the initial presentation of status epilepticus, a directed history suffices. Obtain a more detailed history after stabilization, including the following details:
PhysicalPerform a rapid, directed physical and neurologic examination during status epilepticus, followed by a detailed examination when the child is stabilized.
Causes
DIFFERENTIALSSection 4 of 10
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
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| Drug Name | Lorazepam (Ativan) |
|---|---|
| Description | 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. |
| Adult Dose | 4 mg/dose IV slowly over 2-5 min; repeat in 10-15 min prn; not to exceed 8 mg/dose |
| Pediatric Dose | Infants and children: 0.1 mg/kg IV slowly over 2-5 min; repeat prn in 10-15 min at 0.05 mg/kg; not to exceed 4 mg/dose Adolescents: 0.07 mg/kg IV slowly over 2-5 min; repeat in 10-15 min prn; not to exceed 4 mg/dose |
| Contraindications | Documented hypersensitivity; preexisting CNS depression, hypotension, or narrow-angle glaucoma |
| Interactions | Toxicity of benzodiazepines in CNS increases when used concurrently with alcohol, phenothiazines, barbiturates, and MAOIs |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in renal or hepatic impairment, myasthenia gravis, organic brain syndrome, or Parkinson disease |
| Drug Name | Diazepam (Valium) |
|---|---|
| Description | 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. |
| Adult Dose | 5-10 mg IV q10-20min; not to exceed 30 mg in an 8-h period; may repeat in 2-4 h prn |
| Pediatric Dose | 0.2-0.5 mg/kg/dose IV/IO administered over 2-5 min; repeat q15-30min; not to exceed a total cumulative dose of 10 mg; repeat in 2-4 h prn; alternatively, 0.5 mg/kg PR, then 0.25 mg/kg in 10 min prn |
| Contraindications | Documented hypersensitivity; narrow-angle glaucoma |
| Interactions | Increases CNS toxicity with coadministration of phenothiazines, barbiturates, ethanol, opiates, or MAOIs; cimetidine, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, propanolol, PO contraceptives, propoxyphene, and valproic acid may increase effect of benzodiazepines due to decreased metabolism |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution with other CNS depressants, low albumin levels, or hepatic disease (may increase toxicity); monitor for respiratory depression; may precipitate porphyria attack; monitor for respiratory depression; mild effects on blood pressure and cardiac output may be seen, which may be significant in patients with preexisting cardiac dysfunction; ataxia, irritability, and sedation are common adverse effects; patients occasionally may have psychotic reactions or suicidal ideation after use |
| Drug Name | Midazolam (Versed) |
|---|---|
| Description | 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). |
| Adult Dose | 2.5-5 mg IV once Refractory SE: 200 mcg/kg (0.2 mg/kg) IV bolus infused over 2-5 min, followed by 45-660 mcg/kg/h (0.75-11 mcg/kg/min) continuous IV infusion |
| Pediatric Dose | 0.2 mg/kg IM; or 0.05-0.2 mg/kg IV/IO; may repeat q10-15min; not to exceed a cumulative dose of 10 mg; alternatively, 0.15 mg/kg IV initially, followed 1 mcg/kg/min continuous IV infusion; titrate dose until clinical seizure activity controlled |
| Contraindications | Documented hypersensitivity; preexisting hypotension; narrow-angle glaucoma; sensitivity to propylene glycol (the diluent) |
| Interactions | Sedative effects may be antagonized by theophyllines; opiates and erythromycin may accentuate sedative effects of midazolam due to decreased clearance; increases CNS toxicity with coadministration of phenothiazines, barbiturates, and MAOIs; cimetidine, disulfiram, fluoxetine, isoniazid, ketoconazole, metoprolol, PO contraceptives, propanolol, and valproic acid may increase effect of benzodiazepines |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Caution in CHF, pulmonary disease, renal impairment, and hepatic failure; adverse effects include drowsiness, dizziness, nausea, vomiting, and respiratory depression |
These agents suppress CNS from reticular activating system (presynaptic and postsynaptic).
| Drug Name | Phenobarbital (Barbita, Luminal) |
|---|---|
| Description | 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. |
| Adult Dose | 300-800 mg IV initially, followed by 120-240 mg/dose at 20-min intervals until seizures are controlled or total cumulative dose of 1-2 g is administered |
| Pediatric Dose | 10-20 mg/kg IV infused over 10-15 min in single or divided dose Some patients may require 5 mg/kg/dose q15-30min until seizure is controlled or a cumulative dose of 40 mg/kg is administered |
| Contraindications | Documented hypersensitivity; severe respiratory disease; marked impairment of liver function; severe uncontrolled pain; nephritis |
| Interactions | May decrease effects of chloramphenicol, digitoxin, corticosteroids, carbamazepine, theophylline, verapamil, metronidazole, and anticoagulants (patients stabilized on anticoagulants may require dosage adjustments if added to or withdrawn from their regimen); coadministration with alcohol may produce additive CNS effects and death; chloramphenicol, valproic acid, and MAOIs may increase toxicity; rifampin may decrease effects; induction of microsomal enzymes may result in decreased effects of PO contraceptives in women (must use additional contraceptive methods to prevent unwanted pregnancy; menstrual irregularities may also occur) |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | In prolonged therapy, evaluate hematopoietic, renal, hepatic, and other organ systems; caution in fever, hyperthyroidism, diabetes mellitus, and severe anemia since adverse reactions can occur; caution in myasthenia gravis and myxedema; paradoxical excitement and delirium can occur in infants experiencing pain; may depress mental status significantly |
These agents stabilize neuronal membranes and decrease seizure activity.
| Drug Name | Fosphenytoin (Cerebyx) |
|---|---|
| Description | 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. |
| Adult Dose | Emergent loading dose: 15-20 mg PE/kg IV/IM at 100-150 mg PE/min Nonemergent loading dose: 10-20 mg PE/kg IV/IM at 100 mg PE/min Maintenance dose: 4-6 mg PE/kg/d IV/IM; infusion rate not to exceed 150 mg PE/min to minimize risk of hypotension |
| Pediatric Dose | Loading dose: 15-20 mg PE/kg IV/IM Maintenance dose: 4-7 mg PE/kg IV/IM |
| Contraindications | Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; Adams-Stokes syndrome |
| Interactions | Amiodarone, benzodiazepines, chloramphenicol, cimetidine, disulfiram, ethanol (acute ingestion), omeprazole, phenacemide, phenylbutazone, succinimides, fluconazole, isoniazid, metronidazole, miconazole, sulfonamides, trimethoprim, and valproic acid may increase phenytoin toxicity; may decrease toxicity when taken concurrently with barbiturates, carbamazepine, theophylline, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, and sucralfate; may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, methadone, metyrapone, mexiletine, PO contraceptives, quinidine, theophylline, valproic acid |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Blood dyscrasias have occurred; consequently, perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter; discontinue use if rash appears (if rash is exfoliative, bullous, or purpuric, do not resume use); death from cardiac arrest has occurred after too-rapid IV administration (administer <150 mg/min or <2-3 mg/kg/min) preceded sometimes by marked QRS widening; administer cautiously to patients with acute intermittent porphyria; caution in diabetes (may raise blood sugar levels); discontinue drug if hepatic dysfunction occurs; may cause fetal hydantoin syndrome |
| Drug Name | Phenytoin (Dilantin) |
|---|---|
| Description | 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). |
| Adult Dose | Loading dose: 15-20 mg/kg IV once or divided doses followed by 100-150 mg/dose q30min; infusion rate not to exceed 50 mg/min to avoid hypotension and arrhythmias |
| Pediatric Dose | 18-20 mg/kg IV/IO; infusion rate not to exceed 1 mg/kg/min (infuse over minimum of 20 min) to avoid hypotension and arrhythmias |
| Contraindications | Documented hypersensitivity; sinoatrial block; second- and third-degree AV block; sinus bradycardia; Adams-Stokes syndrome |
| Interactions | Amiodarone, benzodiazepines, chloramphenicol, cimetidine, fluconazole, isoniazid, metronidazole, miconazole, phenylbutazone, succinimides, sulfonamides, omeprazole, phenacemide, disulfiram, ethanol (acute ingestion), trimethoprim, and valproic acid may increase toxicity; effects may decrease when taken concurrently with barbiturates, diazoxide, ethanol (chronic ingestion), rifampin, antacids, charcoal, carbamazepine, theophylline, and sucralfate; may decrease effects of acetaminophen, corticosteroids, dicumarol, disopyramide, doxycycline, estrogens, haloperidol, amiodarone, carbamazepine, cardiac glycosides, quinidine, theophylline, methadone, metyrapone, mexiletine, PO contraceptives, valproic acid |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Perform blood counts and urinalyses when therapy is begun and at monthly intervals for several months thereafter to monitor for blood dyscrasias; discontinue use if a rash appears (do not resume use if rash is exfoliative, bullous, or purpuric); rapid IV infusion (administer <50 mg/min or <1 mg/kg/min) may result in death from cardiac arrest, marked by QRS widening; caution in acute intermittent porphyria and diabetes (may elevate blood sugar levels; discontinue use if hepatic dysfunction occurs; may cause fetal hydantoin syndrome |
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.
| Drug Name | Pentobarbital (Nembutal) |
|---|---|
| Description | 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. |
| Adult Dose | Loading dose: 5-10 mg/kg IV infused slowly over 1-2 h Maintenance: 1 mg/kg/h IV and increase to 2-3 mg/kg/h until EEG inactivity attained |
| Pediatric Dose | Loading dose: 5-10 mg/kg IV/IO infused slowly over 1-2 h; follow with 0.5-3 mg/kg/h continuous IV infusion; maintain burst suppression on EEG |
| Contraindications | Documented hypersensitivity; hypovolemic shock; CHF; hepatic impairment |
| Interactions | Concomitant use with alcohol may produce additive CNS effects and death; chloramphenicol may inhibit metabolism; may enhance chloramphenicol metabolism; MAOIs may enhance sedative effects of barbiturates; valproic acid appears to decrease barbiturate metabolism, increasing toxicity; barbiturates can decrease effects of anticoagulants (patients may require dosage adjustments if barbiturates added to or withdrawn from regimen); decreased contraceptive effect may occur due to induction of microsomal enzymes (alternate form of birth control is suggested); barbiturates may decrease corticosteroid and digitoxin effects through induction of hepatic microsomal enzymes, which increase metabolism; barbiturates decrease theophylline levels, and may decrease effects; may decrease verapamil bioavailability |
| Pregnancy | D - Fetal risk shown in humans; use only if benefits outweigh risk to fetus |
| Precautions | Patient may become tolerant to hypnotic effects; caution in hypovolemic shock, respiratory dysfunction, renal dysfunction, CHF, previous addiction to sedative hypnotics; IV preparations contain 20-40% propylene glycol and up to 10% alcohol (administration of high doses of propylene glycol to infants may be associated with metabolic acidosis) |
Pediatrics, Status Epilepticus excerpt
Article Last Updated: Jun 16, 2008
