Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

ACUTE

generalized convulsive status epilepticus

1st line – supportive care + oxygen

Back
ACUTE
|
generalized convulsive status epilepticus
1st line – 

supportive care + oxygen

Basic life support measures should be initiated, including securing the airway, delivering 100% oxygen by mask or nasal cannula, and correcting hypotension, hyperthermia, glucose and electrolyte abnormalities, and potential thiamine deficiency.[2] Many patients will require a nasopharyngeal airway with oxygen therapy to maintain adequate saturations.[32] 

ECG should be monitored.[34] Cardiac complications are not infrequent and some of the drugs used, particularly phenytoin, can also have cardiac side effects.[19][32]

If the patient is already taking anticonvulsants, the typical therapy should be given at full dose in addition to the emergency treatment.[37] If the dose of anticonvulsants was recently reduced, the changes should be reversed if that is thought to be the cause of SE, as long as it is safe to do so.

Treatment of SE, especially generalized convulsive SE, should be closely monitored at all times in an intensive care setting. This is because the majority of anticonvulsant medications can depress the respiratory and cardiovascular systems.

Plus – thiamine + dextrose (if hypoglycemic)

Back
ACUTE
|
generalized convulsive status epilepticus
Plus – 

thiamine + dextrose (if hypoglycemic)

Treatment recommended for ALL patients in selected patient group

In adults who are hypoglycemic (glucose <60 mg/dL), an intravenous dose of thiamine should be given first, followed by an intravenous bolus of dextrose.[34] In children, thiamine is not usually needed.[34]

Primary options

thiamine (vitamin B1): adults: 100 mg intravenously as a single dose

and

dextrose: children <2 years of age: (12.5% dextrose in water) 4 mL/kg intravenous bolus; children ≥2 years of age: (25% dextrose in water) 2 mL/kg intravenous bolus; adults: (50% dextrose in water) 50 mL intravenous bolus

Plus – benzodiazepine

Back
ACUTE
|
generalized convulsive status epilepticus
Plus – 

benzodiazepine

Treatment recommended for ALL patients in selected patient group

A benzodiazepine is recommended if the seizure continues for 5 minutes or longer.

In hospital settings, intravenous lorazepam is the most commonly used initial therapy.[45] [ Cochrane Clinical Answers logo ] [Evidence B] Intravenous diazepam and intramuscular midazolam are also acceptable first-line treatment options.[34]

In prehospital settings, or where intravenous access or intramuscular midazolam may not be available, rectal diazepam, or buccal or intranasal midazolam, are recommended.[34] Rectal diazepam is commonly given for home use in pediatric epilepsies.[46]

Dose-dependent depression of consciousness and respiratory drive may result from benzodiazepines. For rectal diazepam, lower doses may be needed by patients maintained on barbiturates (to avoid excessive central nervous system depression) and higher doses may be needed by patients on benzodiazepines (because of possible tolerance).

Intravenous lorazepam or diazepam may be repeated once within the first 5 to 20 minutes.[34] Patients should receive a maximum of two doses (including prehospital treatment).[32]

One prospective cohort study of children with refractory convulsive SE showed that delaying benzodiazepine administration beyond 10 minutes after the onset of the seizure was associated with an increased risk of morbidity and mortality.[47]

Primary options

lorazepam: children and adults: 0.1 mg/kg (maximum 4 mg/dose) intravenously as a single dose, may repeat once if necessary

OR

diazepam: children and adults: 0.15 to 0.2 mg/kg (maximum 10 mg/dose) intravenously as a single dose, may repeat once if necessary; children and adults: 0.2 to 0.5 mg/kg (maximum 20 mg/dose) rectally as a single dose

OR

midazolam: children and adults bodyweight 13-40 kg: 5 mg intramuscularly as a single dose; children and adults bodyweight >40 kg: 10 mg intramuscularly as a single dose; children and adults: consult specialist for guidance on intranasal or buccal dose

2nd line – fosphenytoin/phenytoin or valproic acid or levetiracetam or phenobarbital

Back
ACUTE
|
generalized convulsive status epilepticus
2nd line – 

fosphenytoin/phenytoin or valproic acid or levetiracetam or phenobarbital

While there are no studies to guide the timing of second-line therapy, experts advocate second-line therapy following 15 to 20 minutes of seizure activity.[2][34]

Fosphenytoin or phenytoin, valproic acid, levetiracetam, or phenobarbital may be chosen.[49][53]

Fosphenytoin and phenytoin are equally efficacious. Fosphenytoin is a water-soluble prodrug of phenytoin. It is completely converted to phenytoin within 10 to 15 minutes. Fosphenytoin has fewer infusion-related complications but is significantly more expensive.[20] Hypotension and arrhythmias may result from phenytoin and fosphenytoin at high infusion rates.[8] Because phenobarbital may cause adverse events, it should be used as a secondary option if none of the other treatments are available.[34]

In a patient with a small-bore venous catheter, phenytoin infusion may result in venous irritation and tissue damage. Large-bore vascular access is associated with fewer complications.

If the initial dose does not abort SE, additional doses of the selected anticonvulsant drug may be given.

Fosphenytoin, phenytoin, valproic acid (and its derivatives), and phenobarbital are associated with an increased risk of major congenital malformations and neurodevelopmental disorders when used in pregnancy.[58][59]​​ However, this is a relative contraindication, and these drugs may be tried when a mother's life is at risk, after weighing the risk and benefits and specialist consult. Levetiracetam may be the safer option in pregnancy.[58][60][61]​​ 

Primary options

fosphenytoin: children and adults: 20 mg PE/kg (maximum 1500 mg/dose) intravenously as a single dose

More

OR

phenytoin: children and adults: 20 mg/kg (maximum 1500 mg/dose) intravenously as a single dose

More

OR

valproic acid: children and adults: 40 mg/kg (maximum 3000 mg/dose) intravenously as a single dose

OR

levetiracetam: children and adults: 60 mg/kg (maximum 4500 mg/dose) intravenously as a single dose

Secondary options

phenobarbital: children and adults: 15 mg/kg intravenously as a single dose

3rd line – general anesthesia

Back
ACUTE
|
generalized convulsive status epilepticus
3rd line – 

general anesthesia

If seizures continue despite appropriate pharmacotherapy, then rapid sequence induction with general anesthesia should be performed.[37] The patient should be ventilated and placed on continuous electroencephalographic monitoring while general anesthesia is started. Maintenance doses of anticonvulsant medications should be continued.

Midazolam and propofol are often used as initial agents, but other agents may also be used.

Primary options

midazolam: children and adults: consult specialist for guidance on anesthetic dose

OR

propofol: children and adults: consult specialist for guidance on anesthetic dose

Secondary options

pentobarbital: children and adults: consult specialist for guidance on anesthetic dose

4th line – specialist referral

Back
ACUTE
|
generalized convulsive status epilepticus
4th line – 

specialist referral

Super-refractory status epilepticus (SRSE) is defined as SE that continues or recurs 24 hours or more after the onset of anesthetic therapy or recurs on the reduction/withdrawal of anesthesia.[56][57]​ At this time, there is insufficient evidence to suggest favoring the use of any particular anticonvulsants, inhalational agents, or adjunctive treatments over others in SRSE, as data is limited to case series and case reports with substantial confounding factors.[4]​ A specialist should be consulted for advice on management of SRSE.

nonconvulsive status epilepticus

1st line – supportive care + oxygen

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: adults
1st line – 

supportive care + oxygen

Basic life support measures should be initiated, including securing the airway, delivering 100% oxygen by mask or nasal cannula, and correcting hypotension, hyperthermia, glucose and electrolyte abnormalities, and potential thiamine deficiency.[2] Many patients will require a nasopharyngeal airway with oxygen therapy to maintain adequate saturations.[32] 

The patient's ECG should be monitored.[34] Cardiac complications are not infrequent and some of the drugs used, particularly phenytoin, can also have cardiac side effects.[19][32]

If the patient is already taking anticonvulsants, the typical therapy should be given at full dose in addition to the emergency treatment.[37] If the dose of anticonvulsants was recently reduced, the changes should be reversed if that is thought to be the cause of SE, as long as it is safe to do so.

Treatment of SE should be closely monitored at all times in an intensive care setting because the majority of anticonvulsant medications can depress the respiratory and cardiovascular systems.

Plus – thiamine + dextrose (if hypoglycemic)

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: adults
Plus – 

thiamine + dextrose (if hypoglycemic)

Treatment recommended for ALL patients in selected patient group

In adults who are hypoglycemic (glucose <60 mg/dL), an intravenous dose of thiamine should be given first, followed by an intravenous bolus of dextrose.[34]

Primary options

thiamine (vitamin B1): 100 mg intravenously as a single dose

and

dextrose: (50% dextrose in water) 50 mL intravenous bolus

Plus – benzodiazepine

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: adults
Plus – 

benzodiazepine

Treatment recommended for ALL patients in selected patient group

There is a lack of clear, evidence-based guidance for the management of nonconvulsive SE.[20] In clinical practice, the treatment is similar to that for generalized convulsive SE; however, the choice of drug and decision when to escalate to the next level of treatment should be carefully considered within the clinical context. The recommendations detailed here are based on guidelines for generalized convulsive SE.[34]

A benzodiazepine is the first-line treatment recommended if the seizure continues for 5 minutes or longer.

Lorazepam is commonly used if intravenous access is available, with intravenous diazepam as an alternative. Intramuscular midazolam can be administered rapidly and is safe and effective in the prehospital setting. Intramuscular midazolam may have superior effectiveness compared with intravenous lorazepam in adults without established intravenous access. Diazepam is available as a rectal gel and may be given if there is no intravenous access and intramuscular midazolam cannot be administered.[34] Intranasal or buccal midazolam are also alternatives (if available) and intravenous access is not available.

Dose-dependent depression of consciousness and respiratory drive may result from benzodiazepines. For rectal diazepam, lower doses may be needed by patients maintained on barbiturates (to avoid excessive central nervous system depression) and higher doses may be needed by patients on benzodiazepines (because of possible tolerance).

Primary options

lorazepam: 0.1 mg/kg (maximum 4 mg/dose) intravenously as a single dose, may repeat once if necessary

OR

diazepam: 0.15 to 0.2 mg/kg (maximum 10 mg/dose) intravenously as a single dose, may repeat once if necessary; 0.2 to 0.5 mg/kg (maximum 20 mg/dose) rectally as a single dose

OR

midazolam: bodyweight 13-40 kg: 5 mg intramuscularly as a single dose; bodyweight >40 kg: 10 mg intramuscularly as a single dose; consult specialist for guidance on intranasal or buccal dose

2nd line – fosphenytoin/phenytoin or valproic acid or levetiracetam or phenobarbital

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: adults
2nd line – 

fosphenytoin/phenytoin or valproic acid or levetiracetam or phenobarbital

There is no evidence-based or preferred second-line therapy. Fosphenytoin or phenytoin, valproic acid, levetiracetam, or phenobarbital may be chosen.[49][53]

Fosphenytoin and phenytoin are equally efficacious. Fosphenytoin is a water-soluble prodrug of phenytoin. It is completely converted to phenytoin within 10 to 15 minutes. Fosphenytoin has fewer infusion-related complications but is significantly more expensive.[20] Hypotension and arrhythmias may result from phenytoin and fosphenytoin at high infusion rates.[8] 

In a patient with a small-bore venous catheter, phenytoin infusion may result in venous irritation and tissue damage. Large-bore vascular access is associated with fewer complications.

Because phenobarbital may cause adverse events, it should be used as a secondary option if none of the other treatments are available.[34]

If the initial dose does not abort SE, additional doses of the selected anticonvulsant drug may be given.

Fosphenytoin, phenytoin, valproic acid (and its derivatives), and phenobarbital are associated with an increased risk of major congenital malformations and neurodevelopmental disorders when used in pregnancy.[58][59]​​ However, this is a relative contraindication, and these drugs may be tried when a mother's life is at risk, after weighing the risk and benefits and specialist consult. Levetiracetam may be the safer option in pregnancy.[58][60][61]​​ 

Primary options

fosphenytoin: 20 mg PE/kg (maximum 1500 mg/dose) intravenously as a single dose

More

OR

phenytoin: 20 mg/kg (maximum 1500 mg/dose) intravenously as a single dose

More

OR

valproic acid: 40 mg/kg (maximum 3000 mg/dose) intravenously as a single dose

OR

levetiracetam: 60 mg/kg (maximum 4500 mg/dose) intravenously as a single dose

Secondary options

phenobarbital: 15 mg/kg intravenously as a single dose

3rd line – general anesthesia

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: adults
3rd line – 

general anesthesia

If seizures continue despite appropriate pharmacotherapy, rapid sequence induction with general anesthesia should be performed.[37]

The patient should be ventilated and placed on continuous electroencephalographic monitoring while general anesthesia is started. Maintenance doses of anticonvulsant medications should be continued.

Midazolam and propofol are often used as initial agents, but other agents also may be used.

Primary options

midazolam: consult specialist for guidance on anesthetic dose

OR

propofol: consult specialist for guidance on anesthetic dose

Secondary options

pentobarbital: consult specialist for guidance on anesthetic dose

4th line – specialist referral

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: adults
4th line – 

specialist referral

SRSE is defined as SE that continues or recurs 24 hours or more after the onset of anesthetic therapy or recurs on the reduction/withdrawal of anesthesia.[56][57]​​ At this time, there is insufficient evidence to suggest favoring the use of any particular anticonvulsants, inhalational agents, or adjunctive treatments over others in SRSE, as data is limited to case series and case reports with substantial confounding factors.[4]​ A specialist should be consulted for advice on management of SRSE.

1st line – supportive care + oxygen

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: children
1st line – 

supportive care + oxygen

Basic life support measures should be initiated, including securing the airway, delivering 100% oxygen by mask or nasal cannula, and correcting hypotension, hyperthermia, glucose and electrolyte abnormalities, and potential thiamine deficiency.[2] Many patients will require a nasopharyngeal airway with oxygen therapy to maintain adequate saturations.[32] 

The patient's ECG should be monitored.[34] Cardiac complications are not infrequent and some of the drugs used, particularly phenytoin, can also have cardiac side effects.[19][32]

If the patient is already taking anticonvulsants, the typical therapy should be given at full dose in addition to the emergency treatment.[37] If the dose of anticonvulsants was recently reduced, the changes should be reversed if that is thought to be the cause of SE, as long as it is safe to do so.

Treatment of SE should be closely monitored at all times in an intensive care setting because the majority of anticonvulsant medications can depress the respiratory and cardiovascular systems.

Plus – intravenous dextrose (if hypoglycemic)

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: children
Plus – 

intravenous dextrose (if hypoglycemic)

Treatment recommended for ALL patients in selected patient group

In children who are hypoglycemic (glucose <60 mg/dL), an intravenous bolus of dextrose should be administered.[34]

Primary options

dextrose: children <2 years of age: (12.5% dextrose in water) 4 mL/kg intravenous bolus; children ≥2 years of age: (25% dextrose in water) 2 mL/kg intravenous bolus

Plus – benzodiazepine

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: children
Plus – 

benzodiazepine

Treatment recommended for ALL patients in selected patient group

There is a lack of clear, evidence-based guidance for the management of nonconvulsive SE.[20] In clinical practice, the treatment is similar to that for generalized convulsive SE; however, the choice of drug and decision when to escalate to the next level of treatment should be carefully considered within the clinical context. The recommendations detailed here are based on guidelines for generalized convulsive SE.[34]

Benzodiazepines are recommended if the seizure continues for 5 minutes or longer.

Lorazepam is preferred if intravenous access is available, with intravenous diazepam as an alternative. Intramuscular midazolam is preferred if no intravenous access is available. Diazepam is available as a rectal gel and may be given if there is no intravenous access and intramuscular midazolam cannot be administered.[34]

Dose-dependent depression of consciousness and respiratory drive may result from benzodiazepines. For rectal diazepam, lower doses may be needed by patients maintained on barbiturates (to avoid excessive central nervous system depression) and higher doses may be needed by patients on benzodiazepines (because of possible tolerance).

Primary options

lorazepam: 0.1 mg/kg (maximum 4 mg/dose) intravenously as a single dose, may repeat once if necessary

OR

diazepam: 0.15 to 0.2 mg/kg (maximum 10 mg/dose) intravenously as a single dose, may repeat once if necessary; 0.2 to 0.5 mg/kg (maximum 20 mg/dose) rectally as a single dose

OR

midazolam: bodyweight 13-40 kg: 5 mg intramuscularly as a single dose; bodyweight >40 kg: 10 mg intramuscularly as a single dose; consult specialist for guidance on intranasal or buccal dose

2nd line – fosphenytoin/phenytoin or valproic acid or levetiracetam or phenobarbital

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: children
2nd line – 

fosphenytoin/phenytoin or valproic acid or levetiracetam or phenobarbital

There is no evidence-based preferred second-line therapy. Fosphenytoin or phenytoin, valproic acid, or levetiracetam may be chosen.[49][53]

Fosphenytoin and phenytoin are equally efficacious. Fosphenytoin is a water-soluble prodrug of phenytoin. It is completely converted to phenytoin within 10 to 15 minutes. Fosphenytoin has fewer infusion-related complications but is significantly more expensive.[20] Hypotension and arrhythmias may result from phenytoin and fosphenytoin at high infusion rates.[8]

In a patient with a small-bore venous catheter, phenytoin infusion may result in venous irritation and tissue damage. Large-bore vascular access is associated with fewer complications.

Because phenobarbital may cause adverse events, it should be used as a secondary option if none of the other treatments are available.[34]

If the initial dose does not abort SE, additional doses of the selected anticonvulsant drug may be given.

Fosphenytoin, phenytoin, valproic acid (and its derivatives), and phenobarbital are associated with an increased risk of major congenital malformations and neurodevelopmental disorders when used in pregnancy.[58][59]​​ However, this is a relative contraindication, and these drugs may be tried when a mother's life is at risk, after weighing the risk and benefits and specialist consult. Levetiracetam may be the safer option in pregnancy.[58][60][61]​​​

Primary options

fosphenytoin: 20 mg PE/kg (maximum 1500 mg/dose) intravenously as a single dose necessary

More

OR

phenytoin: 20 mg/kg (maximum 1500 mg/dose) intravenously as a single dose

More

OR

valproic acid: 40 mg/kg (maximum 3000 mg/dose) intravenously as a single dose

OR

levetiracetam: 60 mg/kg (maximum 4500 mg/dose) intravenously as a single dose

Secondary options

phenobarbital: 15 mg/kg intravenously as a single dose

3rd line – general anesthesia

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: children
3rd line – 

general anesthesia

If seizures continue despite appropriate pharmacotherapy, rapid sequence induction with general anesthesia should be performed.[37] 

The patient should be ventilated and placed on continuous electroencephalographic monitoring while general anesthesia is started. Maintenance doses of anticonvulsant medications should be continued.

Midazolam and propofol are often used as initial agents, but other agents also may be used.

Primary options

midazolam: consult specialist for guidance on anesthetic dose

OR

propofol: consult specialist for guidance on anesthetic dose

Secondary options

pentobarbital: consult specialist for guidance on anesthetic dose

4th line – specialist referral

Back
ACUTE
|
nonconvulsive status epilepticus
|
generalized or focal with impaired consciousness: children
4th line – 

specialist referral

SRSE is defined as SE that continues or recurs 24 hours or more after the onset of anesthetic therapy or recurs on the reduction/withdrawal of anesthesia.[56][57]​​ At this time, there is insufficient evidence to suggest favoring the use of any particular anticonvulsants, inhalational agents, or adjunctive treatments over others in SRSE, as data is limited to case series and case reports with substantial confounding factors.[4]​ A specialist should be consulted for advice on management of SRSE.​

focal without impaired consciousness

1st line – treatment guided by underlying etiology

Back
ACUTE
|
focal without impaired consciousness
1st line – 

treatment guided by underlying etiology

Because potential causes of focal SE without impaired consciousness are numerous, treatment should be guided by underlying etiology.

Use of anticonvulsants constitutes first-line intervention. These will not abort the focal seizures but will help prevent their propagation. Some physicians prefer use of phenytoin and phenobarbital first, but another anticonvulsant may be used.

back arrow

Choose a patient group to see our recommendations

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

Use of this content is subject to our disclaimer