tonic-clonic seizures with persistent postictal depression of neurologic function between seizures; (2) nonconvulsive status epilepticus, a persistent change in behavior or mental processes with continuous epileptiform EEG but without major motor signs; and (3) focal status epilepticus, with or without altered awareness. Convulsive status epilepticus is a life-threatening emergency that requires immediate treatment. Traditionally, convulsive status epilepticus was defined as more than 30 minutes of either (1) continuous seizure activity or (2) two or more sequential seizures without full recovery of consciousness between seizures.
Because persistent seizure activity is believed to cause permanent neuronal injury and because the majority of seizures terminate in 2 to 3 minutes, it is now generally accepted that treatment should be begun when the seizure duration reaches 5 minutes for generalized tonic-clonic seizures and 10 minutes for focal seizures with or without impairment of consciousness. It is noteworthy that convulsive status epilepticus may evolve to nonconvulsive status epilepticus.
The initial treatment of choice is a benzodiazepine, either intravenous lorazepam or diazepam, although there is evidence that intramuscular midazolam may be equally effective. Lorazepam is less lipophilic than diazepam (logP values of 2.4 and 2.8, respectively) and does not undergo as rapid redistribution from brain to peripheral tissues as does diazepam. Clinically effective diazepam concentrations in the brain following an intravenous bolus fall rapidly as the drug exits the central compartment into peripheral fat. Lorazepam has less extensive peripheral tissue uptake, allowing clinically effective concentrations to remain in the central compartment for much longer. Although lorazepam is now used more frequently than diazepam because of the perceived pharmacokinetic advantage, recent appraisals of the clinical data have not found evidence to favor lorazepam. In the prehospital setting, rectal diazepam, intranasal midazolam, or buccal midazolam are acceptable alternative first treatments if the preferred options are not available. If seizures continue, a second therapy is administered. Intravenous fosphenytoin or phenytoin is most common in the USA, although there is no evidence that these choices are superior to intravenous valproate or levetiracetam. Phenobarbital is also an acceptable second therapy, but it has a long half-life causing persistent side effects including severe sedation, respiratory depression, and hypotension. Lacosamide is available in an intravenous formulation, but there is little published experience to assess its efficacy. If the second therapy fails to stop the seizures, an additional second-line agent is often tried. Refractory status epilepticus occurs when seizures continue or recur at least 30 minutes after treatment with first and second therapy agents. Refractory status epilepticus is treated with anesthetic doses of pentobarbital, propofol, midazolam, or thiopental. Case reports indicate that ketamine may be effective. If status epilepticus continues or recurs 24 hours or more after the onset of anesthesia, the condition is considered super-refractory. Often, super-refractory status epilepticus is recognized when anesthetics are withdrawn and seizures recur. There are no established therapies for super-refractory status epilepticus other than to reinstitute general anesthesia.