Evaluation of intravenous lorazepam dosing strategies and the incidence of refractory status epilepticus

Abstract

IntroductionStatus epilepticus (SE) is a neurological emergency associated with high mortality if not identified and treated promptly. For the emergent treatment of SE, the recommended intravenous (IV) lorazepam dose is 0.1 mg/kg/dose, up to a maximum of 4 mg. It has been shown that lorazepam is commonly under dosed in SE, but there is conflicting data on whether this has a negative impact on patient outcomes. This study assessed any dose less than 4 mg to help identify the effects of under dosing lorazepam in SE. MethodsThis was a retrospective cohort study of patients admitted to a quaternary health system between October 1, 2017 and September 30, 2019 that experienced SE and were initially treated with IV lorazepam. Patients were divided into two cohorts, less than 4 mg or 4 mg, based on the initial one-time dose of lorazepam received. The primary outcome was the proportion of patients that progressed to refractory status epilepticus (RSE) that received an initial IV lorazepam dose of 4 mg compared to less than 4 mg for the treatment of SE. Secondary outcomes evaluated include length of stay, mortality, time in SE, number of seizures, cumulative lorazepam dose prior to urgent therapy, number of lorazepam doses prior to urgent therapy, time to urgent therapy, appropriately dosed urgent therapy, and number of antiepileptic drugs given in SE. ResultsOne hundred twenty patients were included in this study (107 patients received less than 4 mg and 13 patients received 4 mg). All patients included in the study were greater than 40 kg. The primary outcome of progression to RSE was observed in a significantly greater proportion of patients in the less than 4 mg group compared to the 4 mg group (93 [87%] vs. 8 [62%], p = 0.03). There was no difference in hospital or intensive care unit length of stay. However, there was an increased rate of in-hospital mortality in patients who received 4 mg compared to less than 4 mg (5 [39%] vs. 12[11%], p = 0.02). DiscussionThe majority of patients in the study received less than the recommended dose of IV lorazepam for SE. Patients who received less than 4 mg experienced an increased progression to RSE, which supports current guideline recommended dosing. While there was an increased rate of mortality in patients who received 4 mg compared to less than 4 mg, time in SE was prolonged in the patient population and severity of illness was only available for a limited number of patients included.