There is a long list of medications used for RSE that have been described in small series or randomized trials (Table 3-8).
Table 3-8.Alternative Options for Intractable SE ||Download (.pdf) Table 3-8. Alternative Options for Intractable SE
|Antiepileptics ||Immunotherapy ||Others |
|Levetiracetam ||High-dose steroids ||Hypothermia |
|Ketamine ||Immunoglobulins ||Ketotic diet |
|Topiramate ||Plasmapheresis ||Vagal nerve stimulation |
|Lacosamide ||ACTH ||Deep brain stimulation |
|Inhaled anesthetics || ||Transcranial magnetic stimulation |
|Lidocaine || ||Neurosurgical removal |
|Verapamil || ||Electroconvulsive therapy |
Alternative Treatment Options in RSE
Levetiracetam IV was initially approved in 2006 by the Food and Drug Administration (FDA) for patients with epilepsy who could not take oral medication. In a recent retrospective study, IV levetiracetam (mean loading dose of 994 mg over 30 minutes and maintenance dose of 2166 mg/day) was successfully used to treat 16 of 18 episodes of focal SE that were refractory to initial benzodiazepine trial.60 In a second study of 24 critically ill patients with mainly focal-onset seizures and status, up to 82% responded to mean IV loading dose of 1780 mg +/– 649 mg bid with the only side effect of transient thrombocytopenia (4% of the patients).61
Lacosamide, a new AED with both enteral and parenteral forms, was approved by the FDA in October 2008 as adjunctive therapy for partial-onset seizures in adults suffering from epilepsy. Successful use of lacosamide 200-mg bolus over 5 minutes has been reported in only one case of left-hemispheric NCSE.62
In the absence of ileus, enteric topiramate has been used successfully in dosages of 300 to 1600 mg/day to abort RSE to prevent the breakthrough and withdrawal seizures while tapering the continuous IV (cIV) infusions. Other adjunctive oral medications that we and others have used, especially while tapering off the drip, include oxcarbazepine, felbamate, pregabalin, and carbamazepine.
Ketamine is a NMDA-antagonist that has demonstrated positive results in abolishing self-perpetuating SE in animal models.63 Moreover, it seems to have a synergistic effect when combined with benzodiazepines.64 Although little experience exists in the adult population, the dosing has been extrapolated from the anesthesia literature (loading dose 1 to 2 mg/kg IV over 1 minute; maintenance 0.6 to 1.8 mg/kg per hour cIV). It is thought to possess other potential neuroprotective effects. Unlike most of the other agents used for RSE, it also increases blood pressure. Caution should be warranted in patients with elevated ICP, traumatic brain injury (TBI), ocular injuries, hypertension, chronic congestive heart failure (CHF), myocardial infarction (MI), tachyarrhythmias, and history of alcohol abuse.65
Few studies exist on using inhaled anesthetic including isoflurane, halothane, or desflurane. Although it seems to be highly efficacious in terminating RSE, hypotension, logistical issues in most ICU settings, and frequent seizure recurrence upon withdrawal make it a less attractive choice.
Hypothermia: Very little experience exists with this treatment option.66,67 A very small case series of four patients has suggested that induced hypothermia with a target temperature 31°C to 35°C may have a potential antiepileptic effect in terminating SE. In all four patients, the treating physicians were able to stop the cIV midazolam, and two of them remained seizure-free. A potentially beneficial side effect of hypothermia is its neuroprotective properties. Disadvantages include shivering, electrolyte abnormalities, immunosuppression, and potential coagulopathy.
Immunomodulatory agents such as steroid IV, immunoglobulins, plasmapheresis, or adrenonocorticotropic hormone (ACTH) may be helpful; in selected cases of immunologic syndromes such as Rasmussen encephalitis, anti–voltage-gated potassium channel–related limbic encephalitis, acute disseminated encephalomyelitis, and paraneoplastic disorders have occurred. However, the role of these agents outside of identified immune processes is unclear.
Lidocaine (1.5- to 2.0-mg/kg bolus, maintenance dose 3 to 4 mg/kg per hour) was efficacious in terminating seizures in 75% of patients with refractory status after the initial bolus. However, narrow pharmacologic range and neurotoxic side effects (>5 μg/mL) limit its use.68
Some practitioners have also recommended using pyridoxine hydrochloride early on in patients with SE in an IV or enteral form at 100 to 300 mg/day, as it is a cofactor in the synthesis of the inhibitory neurotransmitter GABA, which may play a role in the initial phase of SE.
Surgery: Small series from the pediatric literature support that if a single, identifiable focus exists on EEG and imaging (single-photon emission CT [SPECT] or positron emission tomography [PET]), surgical removal of a focal structural lesion may be an option after intracranial mapping.69
In preparation of a second attempt to titrate the patient off cIV AEDs, levetiracetam 1000 mg IV was loaded and maintenance of 2000 bid was started. Propofol drip was first discontinued owing to hypotension and high norepinephrine requirements. With recurrence of electrographic seizures, ketamine was added and the Versed (midazolam) drip increased to 2 mg/kg per hour and a burst-suppression pattern was seen on cEEG.