Treatment of Convulsive Status Epilepticus in Children and Adults
Publication Date: January 1, 2016
Last Updated: March 14, 2022
Recommendations
Initial and Subsequent Therapy
Adult Studies
In adults, IM midazolam, IV lorazepam, IV diazepam (with or without phenytoin), and IV phenobarbital are established as efficacious at stopping seizures lasting at least 5 minutes. (Level A)
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Intramuscular midazolam has superior effectiveness compared with IV lorazepam in adults with convulsive status epilepticus without established IV access. (Level A)
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Intravenous lorazepam is more effective than IV phenytoin in stopping seizures lasting at least 10 minutes. (Level A)
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There is no difference in efficacy between IV lorazepam followed by IV phenytoin, IV diazepam plus phenytoin followed by IV lorazepam, and IV phenobarbital followed by IV phenytoin. (Level A)
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Intravenous valproic acid has similar efficacy to IV phenytoin or continuous IV diazepam as second therapy after failure of a benzodiazepine. (Level C)
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Insufficient data exist in adults about the efficacy of levetiracetam as either initial or second therapy. (Level U)
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Pediatric Studies
In children, IV lorazepam and IV diazepam are established as efficacious at stopping seizures lasting at least 5 minutes. (Level A)
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Rectal diazepam, IM midazolam, intranasal midazolam, and buccal midazolam are probably effective at stopping seizures lasting at least 5 minutes. (Level B)
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Insufficient data exist in children about the efficacy of intranasal lorazepam, sublingual lorazepam, rectal lorazepam, valproic acid, levetiracetam, phenobarbital, and phenytoin as initial therapy. (Level U)
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Intravenous valproic acid has similar efficacy but better tolerability than IV phenobarbital as second therapy after failure of a benzodiazepine. (Level B)
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Insufficient data exist in children regarding the efficacy of phenytoin or levetiracetam as second therapy after failure of a benzodiazepine. (Level U)
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Adverse Events
Adult Studies
Respiratory and cardiac symptoms are the most common encountered treatment-emergent adverse events associated with IV anticonvulsant administration in adults with status epilepticus, indicating that respiratory problems are an important consequence of untreated status epilepticus. (Level A)
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The rate of respiratory depression in patients with status epilepticus treated with benzodiazepines is lower than in patients with status epilepticus treated with placebo. (Level A)
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No substantial difference exists between benzodiazepines and phenobarbital in the occurrence of cardiorespiratory adverse events in adults with status epilepticus. (Level A)
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Pediatric Studies
Respiratory depression is the most common clinically significant treatment-emergent adverse event associated with anticonvulsant drug treatment in status epilepticus in children. (Level A)
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No substantial difference probably exists between midazolam, lorazepam, and diazepam administration by any route in children with respect to rates of respiratory depression. (Level B)
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Adverse events including respiratory depression, with benzodiazepine administration for status epilepticus have been reported less frequently in children than in adults. (Level B)
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Most Effective Benzodiazepine
Adult Studies
In adults with status epilepticus without established IV access, IM midazolam is established as more effective compared with IV lorazepam. (Level A)
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No significant difference in effectiveness has been demonstrated between lorazepam and diazepam in adults with status epilepticus. (Level A)
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Pediatric Studies
In children with status epilepticus, no significant difference in effectiveness has been established between IV lorazepam and IV diazepam. (Level A)
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In children with status epilepticus, non-IV midazolam (IM/intranasal/buccal) is probably more effective than diazepam (IV/rectal). (Level B)
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IV Fosphenytoin vs. IV Phenytoin
Insufficient data exist about the comparative efficacy of phenytoin and fosphenytoin. (Level U)
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Fosphenytoin is better tolerated compared with phenytoin. (Level B)
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When both are available, fosphenytoin is preferred based on tolerability, but phenytoin is an acceptable alternative. (Level B)
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Duration of Anticonvulsant Efficacy
In adults, the second anticonvulsant administered is less effective than the first “standard” anticonvulsant, while the third anticonvulsant administered is substantially less effective than the first “standard” anticonvulsant. (Level A)
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In children, the second anticonvulsant appears less effective, and there are no data about third anticonvulsant efficacy. (Level C)
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Treatment Process
Initial Therapy Phase
The initial therapy phase should begin when the seizure duration reaches 5 minutes and should conclude by the 20-minute mark when response (or lack of response) to initial therapy should be apparent. A benzodiazepine (specifically IM midazolam, IV lorazepam, or IV diazepam) is recommended as the initial therapy of choice, given their demonstrated efficacy, safety, and tolerability. (Level A)
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Initial therapy should be administered as an adequate single full dose rather than broken into multiple smaller doses. Initial therapies should not be given twice except for IV lorazepam and diazepam that can be repeated at full doses once. (Level A)
- Doses listed in the initial therapy phase are those used in class I trials.
- Note that some consensus guidelines list slightly different dosages; for example, phenobarbital is often recommended at 20 mg/kg.
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Although IV phenobarbital is established as efficacious and well tolerated as initial therapy, its slower rate of administration, compared with the three recommended benzodiazepines above, positions it as an alternative initial therapy rather than a drug of first choice. (Level A)
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For prehospital settings or where the three first-line benzodiazepine options are not available, rectal diazepam, intranasal midazolam, and buccal midazolam are reasonable initial therapy alternatives. (Level B)
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Second Therapy Phase
The second-therapy phase should begin when the seizure duration reaches 20 minutes and should conclude by the 40-minute mark when response (or lack of response) to the second therapy should be apparent. Reasonable options include
- fosphenytoin
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- valproic acid
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- levetiracetam.
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There is no clear evidence that any one of these options is better than the others.
The ongoing Established Status Epilepticus Treatment Trial (ESETT) should provide the answer in the next few years.
The ongoing Established Status Epilepticus Treatment Trial (ESETT) should provide the answer in the next few years.
Because of adverse events, IV phenobarbital is a reasonable second-therapy alternative if none of the three recommended therapies is available. (Level B)
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Third Therapy Phase
The third therapy phase should begin when the seizure duration reaches 40 minutes. There is no clear evidence to guide therapy in this phase. (Level U)
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Compared with initial therapy, second therapy is often less effective than initial therapy,
- adults
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- children
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and the third therapy is substantially less effective than initial therapy.
- adults
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- children
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Recommendation Grading
Overview
Title
Treatment of Convulsive Status Epilepticus in Children and Adults
Authoring Organization
American Epilepsy Society
Publication Month/Year
January 1, 2016
Last Updated Month/Year
June 1, 2023
Document Type
Guideline
External Publication Status
Published
Country of Publication
US
Document Objectives
To analyze efficacy, tolerability and safety data for anticonvulsant treatment of children and adults with convulsive status epilepticus and use this analysis to develop an evidence-based treatment algorithm.
Target Patient Population
Patients with convulsive status epilepticus
Inclusion Criteria
Female, Male, Adolescent, Adult, Child, Older adult
Health Care Settings
Ambulatory, Emergency care, Home health, Hospital, Outpatient
Intended Users
Nurse, nurse practitioner, physician, physician assistant
Scope
Assessment and screening, Management, Treatment
Diseases/Conditions (MeSH)
D013226 - Status Epilepticus, D000927 - Anticonvulsants
Keywords
status epilecticus