The anesthetic drug treatment of refractory and super-refractory status epilepticus around the world: Results from a global audit.

Multinational and multicenter registries collecting cases of refractory and super-refractory status epilepticus help to understand what the current practice in the treatment of such conditions is and can improve the rational therapy. We prospectively collected 776 cases of refractory status epilepticus requiring continuous intravenous anesthetic drugs in an intensive care unit setting, through online questionnaires compiled by the treating physicians in 50 countries. Initiation of an intravenous anaesthetic drug was relatively delayed in middle-income compared with high-income countries. There were marked regional differences in the choice of initial intravenous anaesthetic drug. Generally, midazolam was the most commonly used initial anesthetic drug (56%), followed by propofol (35%), in Europe, propofol was preferred over midazolam. In addition to anesthesia, 26% of cases received some form of immunosuppression (with corticosteroids and/or intravenous immunoglobulin). In this observational study, outcome was not affected by choice or sequence of anesthetic drugs, and nor was the use of barbiturate anesthetics associated with poorer outcome. The proportion of patients responding to cycles of different anaesthetic drugs was high even after failure of the earlier anesthetics, but the neurological outcome progressively worsened the longer anaesthetic drugs were needed and the longer the status epilepticus continued. However, even in the 158 patients who required three or more different anaesthetic trials, 49% had seizure control on tapering the third anesthetic, and 20% had a good neurological outcome anywhere. For these reasons we believe that it is important to persist with therapy in patients who are intractable initially, especially as etiology, not the number of duration of anesthesia, is the primary determinant of prognosis. This article is part of the Special Issue "Proceedings of the 7th London-Innsbruck Colloquium on Status Epilepticus and Acute Seizures".

Etiologies and characteristics of refractory status epilepticus cases in different areas of the world: Results from a global audit.

To describe the demographics, etiologies, types of status epilepticus (SE), and outcomes in people with refractory and super-refractory SE from around the world, we prospectively collected cases of refractory SE (RSE) treated with continuous intravenous anesthetic drugs in an intensive care unit setting through online questionnaires using "active surveillance." We collected information about 776 cases of RSE in 50 countries over 4 years. Control of SE was achieved in 74% of the cases. Neurologic outcomes were poor in 41% of patients, and 24% died. Good outcome was associated with younger age and a history of epilepsy. Etiology strongly influenced the outcome. Patients from Asia were younger, more frequently presented with convulsive SE, and were more frequently affected by infectious etiologies when compared with patients from Europe and the Americas. Despite these differences, outcomes were similar in all countries. Demographics of patients with RSE in a global audit are similar to those in prior single center series, providing evidence of generalizability of those studies. Important differences exist among patients with RSE from different regions of the world, but these do not seem to significantly influence patient outcomes.

Preliminary results of the global audit of treatment of refractory status epilepticus.

The treatment of refractory and super refractory status epilepticus is a "terra incognita" from the point of view of evidence-based medicine. As randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available, we carried out an online multinational audit (registry) in which neurologists or intensivists caring for patients with status epilepticus may prospectively enter patients who required general anesthesia to control the status epilepticus (SE). To date, 488 cases from 44 different countries have been collected. Most of the patients had no history of epilepsy and had a cryptogenic etiology. First-line treatment was delayed and not in line with current guidelines. The most widely used anesthetic of first choice was midazolam (59%), followed by propofol and barbiturates. Ketamine was used in most severe cases. Other therapies were administered in 35% of the cases, mainly steroids and immunotherapy. Seizure control was achieved in 74% of the patients. Twenty-two percent of patients died during treatment, and four percent had treatment actively withdrawn because of an anticipated poor outcome. The neurological outcome was good in 36% and poor in 39.3% of cases, while 25% died during hospitalization. Factors that positively influenced outcome were younger age, history of epilepsy, and low number of different anesthetics tried. This article is part of a Special Issue entitled "Status Epilepticus".

What can we learn from status epilepticus registries?

There is a remarkable dearth of information about the various therapies used, often widely so, to control refractory or super-refractory status epilepticus despite its high mortality and morbidity. As pointed out by recent literature reviews, there are no controlled studies, and information is based almost entirely on open, often small and retrospective, case series or case reports. Randomized or controlled studies that are sufficiently powered are not feasible in relation to the many therapies and treatment approaches available. For this reason, we proposed an international case registry of therapies used in refractory and super-refractory cases and their outcome. Clinicians from different countries will be asked to complete an online questionnaire when they treat a patient with refractory or super-refractory status epilepticus. Information gathered from this database will summarize the spectrum of etiologies, treatments, and outcomes of this challenging condition and may even form the bases for treatment guidelines or future targeted treatment trials.