Treat status epilepticus

Step 1. Give a benzodiazepine

Start drug treatment:

  • after 5 minutes of continuous seizure activity, or
  • when the patient has repeated seizures without full recovery of consciousness between attacks.

Manage status epilepticus as a medical emergency. Most patients need to be intubated.

For seizures in children, in addition to the advice that follows, see febrile seizures, infantile spasms and neonatal seizures.

If intravenous access is available quickly, use:

1 midazolam 10 mg (child: 0.15 to 0.2 mg/kg up to 10 mg) intravenously, over at least 2 minutes status epilepticus midazolam    

OR

2 diazepam 10 mg (child: 0.1 to 0.25 mg/kg up to 10 mg) intravenously, over at least 2 minutes status epilepticus diazepam    

OR

3 clonazepam 1 mg (child: 0.25 to 0.5 mg) intravenously, over at least 2 minutes. status epilepticus clonazepam    

If intravenous access cannot be obtained quickly, use:

1 midazolam, adult over 40 kg, 10 mg; adult under 40 kg, 5 mg (child: 0.15 to 0.2 mg/kg up to 10 mg) intramuscularly midazolam    

OR

2 midazolam 5 to 10 mg (child: 0.2 to 0.3 mg/kg up to 10 mg) buccally or intranasally1. midazolam    

Step 2. Give an antiepileptic drug

If the seizure stops promptly and the cause has been identified and reversed (see acute symptomatic seizures), further treatment is not needed. In all other patients, prevent further acute seizures by starting treatment with an antiepileptic drug—the benzodiazepines recommended in Step 1 have a short anticonvulsant effect.

If the patient usually takes an antiepileptic drug(s) for epilepsy, the choice of drug in this step depends on several clinical variables—seek expert advice.

In adults, levetiracetam and sodium valproate are the preferred antiepileptic drugs to prevent further acute seizures after benzodiazepine administration (see Step 1). In a randomised controlled trial, levetiracetam, sodium valproate and phenytoin were found to be equally efficacious at the doses recommended below2; however, phenytoin is not preferred because of its adverse effect profile (eg arrhythmia, infusion problems, hypotension) and requirement for a slow infusion rate.

For adults, if intravenous access is available3, use:

1levetiracetam 60 mg/kg up to 4500 mg intravenously, over 5 minutes status epilepticuslevetiracetamlevetiracetamlevetiracetam

OR

1 sodium valproate 40 mg/kg up to 3000 mg intravenously, over 5 to 10 minutes status epilepticus45 sodium valproate sodium valproate sodium valproate

OR

2 phenytoin sodium 20 mg/kg intravenously, no faster than 50 mg/minute (25 mg/minute in elderly patients and those with comorbidities). Monitor blood pressure and electrocardiogram (if monitor available)67. status epilepticus phenytoin sodium phenytoin phenytoin

In adults, lacosamide can be used to treat status epilepticus, but supporting evidence is limited. Phenobarbital (phenobarbitone) can also be used in adults, though ideally it should be given in an intensive care setting due to the risk of respiratory depression when given after a benzodiazepine.

In children, levetiracetam, phenytoin and sodium valproate are the preferred antiepileptic drugs to prevent further acute seizures after benzodiazepine administration (see Step 1) and have been found to be equally efficacious in clinical trials289. Despite phenytoin's adverse effect profile (eg arrhythmias, infusion problems, hypotension) and requirement for a slow infusion rate, phenytoin is still a preferred antiepileptic drug in children because of extensive experience with its use and because sodium valproate is associated with a risk of hepatotoxicity in children younger than 3 years. Phenobarbital (phenobarbitone) can also be used in children, but it is not preferred because of the risk of respiratory depression when given after a benzodiazepine; ideally phenobarbital should be given in an intensive care setting.

For children, if intravenous access is available3, use:

1levetiracetam 40 mg/kg up to 3000 mg intravenously, over 5 minuteslevetiracetamlevetiracetamlevetiracetam

OR

1 phenytoin sodium 20 mg/kg intravenously, no faster than 25 mg/minute. Monitor blood pressure and electrocardiogram (if monitor available)67 phenytoin sodium phenytoin phenytoin

OR

1 sodium valproate (child 3 years and older) 40 mg/kg intravenously, over 5 to 10 minutes sodium valproate    10

OR

2 phenobarbital (phenobarbitone) 20 mg/kg up to 1000 mg intravenously, no faster than 1 mg/kg/minute (maximum 60 mg/minute). status epilepticus (child) phenobarbital (phenobarbitone) phenobarbital (phenobarbitone) phenobarbital (phenobarbitone)

When the visible signs of seizure have stopped, perform an electroencephalogram (EEG) in all patients who have not fully regained consciousness, to exclude nonconvulsive status epilepticus.

If the seizure stops after giving an antiepileptic drug, see advice on immediate follow-up after a seizure.

Step 3. Transfer to intensive care unit and seek expert advice

If the seizure continues, transfer the patient to the intensive care unit and seek expert advice. Continuous EEG monitoring should be used, if available.

Deciding when to escalate therapy to an anaesthetic drug with artificial ventilation depends on several clinical factors and the skill set of available personnel. Ongoing seizures with airway or respiratory compromise should prompt early escalation, to minimise the risk of injury to the central nervous system.

As a general guide, an infusion of a general anaesthetic (eg thiopentone, propofol) should be started in patients who are still having seizures after 15 minutes, despite treatment with a benzodiazepine and an antiepileptic drug. Evidence to guide the choice of drug is lacking. When patients are ventilated, avoid long-acting neuromuscular blocking drugs if possible, because these can mask ongoing seizures.

1 Midazolam solution for injection (hydrochloride salt) can be given buccally or intranasally and may be provided under expert advice to parents and carers who have been trained in its use. Fact sheets that explain the method are available (eg from the Royal Children's Hospital Melbourne).Return
2 Chamberlain JM, Kapur J, Shinnar S, Elm J, Holsti M, Babcock L, et al. Efficacy of levetiracetam, fosphenytoin, and valproate for established status epilepticus by age group (ESETT): a double-blind, responsive-adaptive, randomised controlled trial. Lancet 2020;395(10231):1217-24. https://www.ncbi.nlm.nih.gov/pubmed/32203691Return
3 When intravenous access is unobtainable, these drugs can be given intraosseously.Return
4 Sodium valproate is highly teratogenic (see Teratogenic and neurodevelopmental effects of antiepileptic drugs). In pregnant people or people of childbearing potential, levetiracetam is preferred for status epilepticus; however, if levetiracetam is not readily available, administer sodium valproate or phenytoin without delay.Return
5 Sodium valproate may increase the risk of neurodevelopmental disorders in children born to males of reproductive potential; see Sodium valproate use in males of reproductive potential.Return
6 Use phenytoin with caution when status epilepticus is due to overdose with a cardiotoxic drug (eg a tricyclic antidepressant). Specific antidotes or treatments may be indicated in certain cases (eg pyridoxine for isoniazid poisoning). Seek expert toxicology advice. To treat seizures caused by a drug overdose, see specific pharmacological therapies in the Toxicology and toxinology guideline.Return
7 Administer phenytoin undiluted in a syringe driver, if available. If a syringe driver is not available, dilute the phenytoin sodium in sodium chloride 0.9% to 5 mg/mL. The diluted solution must be used within 1 hour to avoid precipitation. After injection, flush the needle or catheter with sodium chloride 0.9% to avoid local venous irritation. Phenytoin is incompatible with other infusion fluids, due to the risk of precipitation.Return
8 Dalziel SR, Borland ML, Furyk J, Bonisch M, Neutze J, Donath S, et al. Levetiracetam versus phenytoin for second-line treatment of convulsive status epilepticus in children (ConSEPT): an open-label, multicentre, randomised controlled trial. Lancet 2019;393(10186):2135-45. https://www.ncbi.nlm.nih.gov/pubmed/31005386Return
9 Lyttle MD, Rainford NEA, Gamble C, Messahel S, Humphreys A, Hickey H, et al. Levetiracetam versus phenytoin for second-line treatment of paediatric convulsive status epilepticus (EcLiPSE): a multicentre, open-label, randomised trial. Lancet 2019;393(10186):2125-34. https://www.ncbi.nlm.nih.gov/pubmed/31005385Return
10 Sodium valproate should be avoided in children younger than 3 years of age because of an increased risk of hepatotoxicity in this age group.Return