Optimization of benzodiazepine use for status epilepticus in the emergency department

Benzodiazepine (BZD) underdosing in status epilepticus (SE) occurs frequently due to perceived risk of respiratory or cardiovascular complications, despite data supporting the guideline-recommended doses of BZDs and evidence that untreated SE carries higher complication rates. The purpose of this study was to determine the incidence of treatment escalation in patients receiving lower than recommended BZD doses (underdosed group) compared with those who received at or above guideline-recommended doses (guideline-dosed group).

This is a single-center retrospective analysis of adults presenting to the emergency department with SE who received BZDs as initial therapy. The primary outcome was incidence of treatment escalation, defined as endotracheal intubation (or attempted intubation) or need for a non-BZD second-line anti-seizure medication for ongoing seizure activity, between the underdosed group versus the guideline-dosed group. Secondary outcomes included hospital length of stay (LOS), intensive care unit (ICU) LOS, ventilator dependent days (VDD), and incidence of BZD-related adverse events. Multivariate logistic regression was used to identify predictors for treatment escalation.

One hundred forty-four patients met inclusion criteria (mean age 52 years; predominantly male). Based on initial BZD dose, 127 (88.2%) were categorized as underdosed and 17 (11.8%) as guideline-dosed. Patients in the underdosed group were significantly more likely to require treatment escalation (69.3% vs 41.2%; p = 0.029) and had significantly longer hospital LOS (p = 0.043) and ICU LOS (p = 0.009). A separate analysis of cumulative BZD administered within 20 min of the initial dose showed no significant differences between groups in treatment escalation, hospital LOS, ICU LOS, or VDD. Incidence of BDZ-related adverse events did not differ between groups in either analysis. Significant predictors for treatment escalation included an initial BZD dose below guideline recommendations, lower initial Glasgow Coma Scale (GCS), and past history of epilepsy.

Initial BZD underdosing in SE was associated with a higher rate of treatment escalation, and longer hospital and ICU LOS, without reducing adverse events. In this sample, underdosing appeared to be associated with adverse clinical consequences rather than improved safety. Though future studies are warranted into the reasoning for underdosing and evaluation of confounders which may impact results, our data demonstrate very few patients reach guideline recommended benzodiazepine dosing. Prioritizing guideline-recommended initial dosing may help minimize treatment escalation and reduce prolongation of care.