Recommendations
Urgent
Aim to achieve seizure control within the first 1 to 2 hours after onset of symptoms as this will significantly affect the prognosis.[24] The earlier treatment of status epilepticus is instituted, the more likely it is to be successful.[19]
Urgent: in hospital
Provide resuscitation and immediate emergency treatment to prevent neurological damage and death.[1] Once you have excluded non-epileptic seizures (i.e., dissociative seizures), do not delay treatment by waiting to take samples or receive results.
Immediate management (stabilisation)
Note the time. Call for help.[19]
Take an Airway, Breathing, Circulation (ABC) approach.[19] In particular:
Secure the airway (place the patient in a semi-prone position to avoid aspiration; use a nasopharyngeal airway)[19]
Give high-concentration oxygen.[19]
Start regular monitoring, which may include:
Neurological observations. Use the Glasgow Coma Scale (GCS) [ Glasgow Coma Scale Opens in new window ]
If GCS score ≤8 (i.e., patient not obeying commands, not speaking, not eye opening) request an urgent intensive care unit review for appropriate airway management[38]
Pulse, blood pressure, temperature[19]
ECG[29]
Biochemistry, blood gases, clotting, full blood count[19][22]
Anticonvulsant levels.[19]
Give:
Thiamine (vitamin B1) if there is any suggestion of alcohol abuse or impaired nutrition.[29] Do this before or at the same time as glucose.
Glucose if the patient is hypoglycaemic.[19]
Treat severe acidosis if present.
Early status epilepticus (first-line anticonvulsant therapy)
Check whether any pre-hospital treatment has been given.
If the patient has an individualised emergency management plan that is immediately available, administer medication as detailed in the plan.[1] Give the patient's usual anticonvulsant therapy (if they are already taking this for known epilepsy) in parallel with emergency treatment.[39]
If no emergency management plan is immediately available:[1]
If two adequate doses of any benzodiazepine (e.g., lorazepam, midazolam, diazepam) have been given and seizures have not stopped, go straight to Established status epilepticus (second-line anticonvulsant therapy) below.[1]
If benzodiazepines have not already been administered in the community, give intravenous lorazepam as first-line treatment if intravenous access and resuscitation facilities are immediately available; maximum of two doses (including pre-hospital).[1]
If convulsive status epilepticus does not respond to the first dose of benzodiazepine:[1]
Seek expert guidance
Continue to follow the patient's individualised emergency management plan, if this is immediately available, or give a second dose of benzodiazepine if the seizure does not stop within 5 to 10 minutes of the first dose.
Established status epilepticus (second-line anticonvulsant therapy)
If seizures continue despite two doses of a benzodiazepine, the National Institute for Health and Care Excellence (NICE) in the UK recommends to give one of the following second-line intravenous anticonvulsants:[1]
If convulsive status epilepticus does not respond to a second-line treatment, consider trying an alternative second-line treatment option under expert guidance.[1]
Refractory status epilepticus (third-line therapy)
If convulsive status epilepticus does not respond to second-line treatment options (e.g., levetiracetam, phenytoin, sodium valproate), a specialist may recommend transfer to intensive care for phenobarbital or general anaesthesia.[1]
Urgent: in the community
Note the time.
If the patient has an individualised emergency management plan that is immediately available, administer medication as detailed in the plan.[1]
If an emergency management plan is not immediately available, give buccal midazolam or rectal diazepam immediately as first-line treatment.[1]
If convulsive status epilepticus does not respond to the first dose of benzodiazepine:[1]
Call emergency services
Either continue to follow the patient's emergency management plan (if immediately available) or give a second dose of benzodiazepine if the seizure does not stop within 5 to 10 minutes of the first dose.
Give supportive care as needed, if the facilities are available. In particular:[40]
Secure the airway: consider a nasopharyngeal airway
Give high-concentration oxygen.
Key Recommendations
[Figure caption and citation for the preceding image starts]: Convulsive status epilepticus: key diagnostic and management recommendations flowchart. BP, blood pressure; Ca, calcium; CRP, C-reactive protein; ECG, electrocardiogram; EEG, electroencephalogram; FBC, full blood count; GCS, Glasgow Coma Scale; ICU, intensive care unit; Mg, magnesium; Na, sodiumCreated by the BMJ Knowledge Centre based on key references (see references page) [Citation ends].
If you suspect non-convulsive status epilepticus, refer the patient to the neurology team for specialist clinical assessment and management (recommendation based on clinical experience).
Provide resuscitation and immediate emergency treatment to prevent neurological damage and death.[1] Once you have excluded non-epileptic seizures (dissociative seizures), do not delay treatment by waiting to take samples or receive results. The longer the duration of convulsive status epilepticus, the worse the prognosis.[19]
Aim to achieve seizure control within the first 1 to 2 hours after onset of seizures.[24]
Immediate management (stabilisation)
Note the time. Call for help.[19]
Seek help early to carry out management steps in parallel with other members of the multidisciplinary team.[19]
Take an Airway, Breathing, Circulation (ABC) approach.[19] In particular:
Secure the airway (place the patient in a semi-prone position to avoid aspiration; use a nasopharyngeal airway)[19]
Give high-concentration oxygen.
Start regular monitoring, which may include:
Neurological observations. Use the Glasgow Coma Scale (GCS) [ Glasgow Coma Scale Opens in new window ]
If GCS score ≤8 (i.e., patient not obeying commands, not speaking, not eye opening) request an urgent review by the intensive care team for appropriate airway management[38]
Pulse[19]
Blood pressure[19]
Temperature[19]
ECG[29]
Biochemistry, blood gases, clotting, blood count.[19]
Anticonvulsant levels.[19]
Seek advice from the neurology team to guide decisions on which anticonvulsant concentrations to monitor regularly.
The National Institute for Health and Care Excellence in the UK recommends to consider monitoring of anticonvulsant drug levels during treatment for status epilepticus.[1] However, in practice this is not done routinely. This is because anticonvulsant drug concentrations may exceed the published target concentrations. Bear in mind that regular monitoring may be useful to confirm adequate levels of anticonvulsant before an agent is considered ineffective in patients with refractory status epilepticus.
Give thiamine (vitamin B1) if there is any suggestion of alcohol abuse or impaired nutrition.[29]
Usually administered as a high-potency vitamin B preparation (e.g., Pabrinex® in the UK).
In practice, thiamine is administered before or at the same time as glucose (particularly in those who are at risk for thiamine deficiency) to avoid Wernicke’s encephalopathy.[41]
Give glucose if the patient is hypoglycaemic.[19]
Treat severe acidosis if present.
Practical tip
In practice, do not wait until the patient is in status epilepticus to start emergency treatment (as long as you have excluded non-epileptic seizures) in patients with impending status (i.e., those who are having seizures of increasing frequency and duration). It is easier to reverse at this stage than when the patient goes into status epilepticus.
Early status epilepticus: first-line anticonvulsant therapy
Check whether any pre-hospital treatment has been given.
If the patient has an individualised emergency management plan that is immediately available, administer medication as detailed in the plan.[1] Give the patient's usual anticonvulsant therapy (if they are already taking this for known epilepsy) in parallel with emergency treatment.[39]
If no emergency management plan is immediately available:[1]
If two adequate doses of any benzodiazepine (e.g., lorazepam, midazolam, diazepam) have been given and seizures have not stopped, go straight to Established status epilepticus: second-line anticonvulsant therapy below.[1]
If benzodiazepines have not already been administered in the community, give intravenous lorazepam as first-line treatment if intravenous access and resuscitation facilities are immediately available; maximum of two doses (including pre-hospital).[1]
If convulsive status epilepticus does not respond to the first dose of benzodiazepine:[1]
Seek expert guidance
Continue to follow the patient's individualised emergency management plan, if this is immediately available, or give a second dose of benzodiazepine if the seizure does not stop within 5 to 10 minutes of the first dose.
Practical tip
Follow your local protocol regarding doses and frequency of benzodiazepine therapy. High doses (above those recommended in protocols) can cause reduced consciousness and respiratory depression. However, be aware that the biggest risk to respiratory function in status epilepticus is ongoing seizures, as opposed to respiratory depression from benzodiazepines.[19]
A Cochrane review found that intravenous lorazepam was more effective than intravenous diazepam in terms of cessation of seizures.[42]
[ 
]
[Evidence B]
Evidence: Intravenous lorazepam in convulsive status epilepticus in a hospital setting
Intravenous lorazepam is recommended as initial treatment of convulsive status epilepticus in adults in a hospital setting.
The National Institute for Health and Care Excellence (NICE) in the UK recommends using intravenous lorazepam as the first-line treatment for convulsive status epilepticus for adults in hospital without an individualised emergency management plan and where intravenous access and resuscitation facilities are immediately available.[1]
Most of the evidence for first-line monotherapy was from trials in children with convulsive status epilepticus (15 studies), with only 3 trials in adults and 2 trials in a mixed population of adults and children.
The guideline committee agreed, based on their clinical experience and expertise, that it was appropriate to consider all the evidence together and make a recommendation for adults and children as the treatment decisions are similar.
All outcomes in the evidence review were considered critical for decision making.
Benefits included time to seizure cessation, quality of life, and healthcare resource use.
Harms included mortality, seizure recurrence, length of hospital stay, intensive care admission, length of intensive care stay, and adverse events (respiratory depression, hypotension, endotracheal intubation, and neuropsychological events, e.g., confusion).
The evidence for first-line monotherapy showed an overall benefit for benzodiazepines; however, there was not enough evidence for the guideline committee to recommend one drug over another.
Speed of delivery was therefore considered to be more important than the type of benzodiazepine.
The committee also discussed that route of administration would depend on setting, and that in hospital intravenous lorazepam should be the initial choice of benzodiazepine due to its rapid action and because it has less of a sedative effect.
Established status epilepticus: second-line anticonvulsant therapy
If seizures continue despite two adequate doses of a benzodiazepine, NICE recommends to give one of the following second-line intravenous anticonvulsants:[1]
Levetiracetam may be quicker to administer and have fewer adverse effects than the alternative options recommended by NICE[1]
Use of levetiracetam is off-label for this indication in the UK
Phenytoin[34]
Although not universally available, fosphenytoin is also an option for convulsive status epilepticus that is refractory to benzodiazepines and is typically preferred by experts in practice.
Fosphenytoin, a water soluble prodrug of phenytoin, has a number of comparative advantages including fewer infusion site reactions, and availability of an intramuscular formulation allowing for potentially quicker and easier administration.[6][19]
If convulsive status epilepticus does not respond to a second-line treatment, consider trying an alternative second-line treatment option under expert guidance.[1]
The choice of second-line anticonvulsant depends on:[19][34]
Availability and your local protocols
The type of epilepsy the patient has and their prescribed medication (where applicable and known)
Poor adherence is a common cause of status epilepticus in people with epilepsy; reloading with the same anticonvulsant may be preferable[9]
Contraindications (e.g., sodium valproate is contraindicated in most women of childbearing age)
Previously ineffective alternatives.
If convulsive status epilepticus does not respond to a second-line treatment, consider trying an alternative second-line treatment option under expert guidance.[1]
Consider vasopressor therapy if needed.[20]
+Evidence: Second-line anticonvulsant treatment
Evidence shows that levetiracetam, sodium valproate, and phenytoin/fosphenytoin are all equally effective and safe to use as second-line anticonvulsant treatment in adults with benzodiazepine-refractory status epilepticus.
National Institute for Health and Care Excellence (NICE) guidelines in the UK recommend phenytoin, sodium valproate, or levetiracetam in convulsive status epilepticus that is refractory to benzodiazepines.[1] In clinical practice, there is consensus that levetiracetam is often the most suitable drug of the three to use in this situation due to ease of administration and side effect profile. However, as the evidence found no significant difference in benefits and harms, the guideline committee recommended any one of the three options to allow individualised, patient-centred care.[1]
The guideline included 21 studies for second-line therapy (9 in adults, 11 in children, and one in a mixed population of adults and children). All patients had convulsive status epilepticus. Most of the evidence was very low quality as assessed by GRADE.
All of the studies were in a hospital setting and the majority used the intravenous route of administration.
Two of the studies included were particularly significant in informing the evidence for the recommendation: Established Status Epilepticus Treatment Trial (ESETT) and Emergency treatment with Levetiracetam or Phenytoin in Status Epilepticus in children (EcLiPSE).[34][43]
Although not recommended by NICE, fosphenytoin is also an option for convulsive status epilepticus that is refractory to benzodiazepines and is typically preferred by experts in practice, if available.
ESETT, a the multicentre double-blind randomised controlled trial (RCT), compared levetiracetam, sodium valproate, and fosphenytoin in people with benzodiazepine-refractory status epilepticus. Results were stratified by age group including 186 adults aged 18-65 years, and 51 older adults aged >65 years.[34]
The study showed similar treatment success rates in those treated with:
Levetiracetam: 44% (95% credible interval 33% to 55%) of adults 18 to 65 years; 37% (19% to 59%) of adults >65 years
Fosphenytoin: 46% (34% to 59%) of adults 18 to 65 years; 35% (17% to 59%) of adults >65 years
Sodium valproate: 46% (34% to 58%) of adults 18 to 65 years; 47% (25% to 70%) of adults >65 years.
There was no difference by drug in primary safety outcomes (life-threatening hypotension or cardiac arrhythmia) although event rates were very low.
There was also no significant difference in the need for endotracheal intubation within an hour of starting the study drug in adults or older adults.
The authors concluded that any of the three drugs can be considered as a potential choice for second-line treatment of benzodiazepine-refractory status epilepticus.[34]
The ESETT RCT also found similar success rates in children, as did the open-label EcLiPSE study comparing levetiracetam with phenytoin.[43]
Refractory status epilepticus (third-line therapy)
If convulsive status epilepticus does not respond to second-line treatment options (e.g., levetiracetam, phenytoin, sodium valproate), a specialist may recommend transfer to intensive care (ICU) for phenobarbital or general anaesthesia.[1]
If available, the neurology team will perform EEG monitoring to determine whether the patient’s reduced level of consciousness is seizure- or anticonvulsant-related.[29]
Ongoing management
In practice, neurology or epilepsy specialist advice is required in patients with status epilepticus to inform ongoing management (including choice and duration of treatment with maintenance of anticonvulsant agents), usually within 24 hours from presentation. The exception is those in whom a rapidly reversible cause (e.g., metabolic derangement) has been identified and treated.
Safety of anticonvulsants in pregnancy
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.[44][45] 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 consultation. Levetiracetam may be the safer option in pregnancy.[44][46][47] NICE: epilepsies in children, young people and adults Opens in new window
Discharge
After an episode of convulsive status epilepticus, agree an emergency management plan with the patient if they do not already have one and there is concern that status epilepticus may recur.[1]
Before discharging the patient from hospital, it is good practice to ensure they have a follow-up arranged with the neurology or epilepsy team to check medication and adherence.
For people with first suspected seizure or a seizure recurrence after a period of remission, refer the patient urgently (for an appointment within 2 weeks) to local neurology/epilepsy services.[1] In practice, neurology or epilepsy specialist advice is also required in patients with status epilepticus to inform ongoing management (including choice and duration of treatment with maintenance of anticonvulsant agents), usually within 24 hours from presentation. The exception is those in whom a rapidly reversible cause (e.g., metabolic derangement) has been identified and treated.
Note the time and give first aid to people having a tonic-clonic seizure in the community. In particular:[48]
Protect the patient from injury
Do not restrain the patient or put anything in their mouth
If the seizure stops, check the patient's airway and place them in the recovery position.
If the facilities are available:[40]
Consider a nasopharyngeal airway to secure the airway
Give high-concentration oxygen.
If the patient with convulsive status epilepticus has an individualised emergency management plan that is immediately available, administer medication as detailed in the plan.[1]
If an emergency management plan is not immediately available, give buccal midazolam or rectal diazepam immediately as first-line treatment.[1]
In the UK, NICE recommends buccal midazolam as first choice, with rectal diazepam as an alternative if agreed, based on previous use or if buccal midazolam is unavailable.[49]
If convulsive status epilepticus does not respond to the first dose of benzodiazepine:[1]
Call emergency services
Either continue to follow the patient's emergency management plan (if immediately available), or give a second dose of benzodiazepine if the seizure does not stop within 5 to 10 minutes of the first dose.
After a prolonged non-convulsive seizure (a non-convulsive seizure that continues for more than 2 minutes longer than the patient's usual seizure), agree an emergency management plan with the patient if they do not already have one and there is concern that prolonged non-convulsive seizures may recur.[1]
Refer the patient to the neurology team for specialist clinical assessment and management (recommendation based on clinical experience).
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