Midazolam and thiopental for the treatment of refractory status epilepticus: a retrospective comparison of efficacy and safety

Abstract

Current management guidelines for refractory status epilepticus (RSE) recommend the use of intravenous continuous anesthetic therapy, but there is little evidence to guide the selection of the most efficacious and safest drug. We conducted a retrospective study to evaluate the efficacy and safety of midazolam versus thiopental for treatment of RSE. Retrospective case-control series of prospectively identified patients treated with midazolam or thiopental for RSE between January 2007 and December 2014. The primary outcome was control of RSE. Secondary outcomes included the rate of adverse events, intensive care unit (ICU) and hospital length of stay, hospital mortality and long-term neurological outcome, assessed with the extended Glasgow outcome scale (GOS-E) at discharge and at six 6 months. A total of 33 patients were included, 19 treated with midazolam and 14 with thiopental. Groups were similar for demographic data, clinical variables, comorbidity and the underlying cause of RSE. The rate of control of SE did not differ between groups (63 vs. 64 %). Adverse events including hypotension (mean arterial pressure <70 mmHg) requiring vasopressors, infections, anemia requiring red blood cells transfusion, leucopenia (<4000/mm(3)), and hyponatremia (<130 mEq/l) were more frequent during thiopental infusion. Furthermore, patients treated with midazolam had a shorter median ICU length of stay (6 vs. 15 days; p = 0.02) and better GOS-E at 6 months (8 [8] vs. 4 [4, 5]; p = 0.01). These findings suggest that continuous midazolam administration is as efficacious as thiopental infusion for the treatment of RSE; however, midazolam was associated with a significantly lower number of adverse events. These findings should be confirmed in larger multicenter trials.

Long‐term outcomes of status epilepticus: A critical assessment

“…Especially pentobarbital has been linked to the development of hypotension requiring prolonged duration of mechanical ventilation and vasopressor therapies,76 which have in turn been associated with poor long‐term outcome 54. Continuous infusion of thiopental was also associated with more frequent adverse events and worse outcome at 6 months compared to continuous infusions of midazolam 77. However, it is discussed whether the association with negative outcomes is effectively due to the use of IVADs, or due to confounding by indication, as patients who require continuous infusions are probably more critically ill 78.…”

Risk score predictive of mortality in status epilepticus according to a national database

“…Although the STESS model requires seizure type and EEG information in case of nonconvulsive SE and EMSE model is more complicated, requires relatively more time and always needs advanced imaging/EEG to fulfill the model, our mode is less time-consuming to use. 20 These findings indicate that anemia may be a predictor of refractory SE. The independent comorbidities were heart disease, central nervous system (CNS) infection, cancer, chronic renal failure, and anemia, whereas the significant SE complications were shock, acute renal failure, septicemia, pneumonia, and respiratory failure.…”

“…Without EEG, there were 3 mainly clinical factors for SE mortality including advanced age, comorbidities, and the presence of SE complications. 20 Neither the STESS model nor the EMSE model includes complications of SE. Advanced age has been reported to be the predictor for SE mortality in several studies including both those that use STESS and those that use EMSE predictive models.…”

Duration of therapeutic coma and outcome of refractory status epilepticus

“…Similar to our cohort, the duration of TC in all these studies had a relatively wide range of treatment duration anywhere from 24 to 96 hours. The rate of seizure recurrence following treatment with TC was found to be between 10% and 20%, but none of these studies looked at seizure recurrence in association with duration of TC . Only one study analyzed the association between duration of TC and various clinical outcomes, and found that treatment duration for greater than 20 hours was associated with poor functional outcome and death .…”

“…T 2 is the second time point at which the dose of anesthetic started to develop a significant downward trend, defined by a drop of at least 20% of the hourly infusion rate in three subsequent hours and an ultimate endpoint of 0 (Figure ). Similar to prior studies comparing the efficacy and safety of different anesthetics, the maximum steady dose of anesthetic was converted to a time‐ and weight‐based unit (µg/kg/min) across all anesthetic agents utilized in the first trial of TC …”