Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial

Abstract

Objective This study was undertaken to describe patterns of benzodiazepine use as first‐line treatment of status epilepticus (SE) and test the association of benzodiazepine doses with response to second‐line agents in patients enrolled in the Established Status Epilepticus Treatment Trial (ESETT). Methods Patients refractory to an adequate dose of benzodiazepines for the treatment of SE were enrolled in ESETT. Choice of benzodiazepine, doses given prior to administration of second‐line agent, route of administration, setting, and patient weight were characterized. These were compared with guideline‐recommended dosing. Logistic regression was used to determine the association of the first dose of benzodiazepine and the cumulative benzodiazepine dose with the response to second‐line agent. Results Four hundred sixty patients were administered 1170 doses of benzodiazepines (669 lorazepam, 398 midazolam, 103 diazepam). Lorazepam was most frequently administered intravenously in the emergency department, midazolam intramuscularly or intravenously by the emergency medical services personnel, and diazepam rectally prior to ambulance arrival. The first dose of the first benzodiazepine (N = 460) was lower than guideline recommendations in 76% of midazolam administrations and 81% of lorazepam administrations. Among all administrations, >85% of midazolam and >76% of lorazepam administrations were lower than recommended. Higher first or cumulative benzodiazepine doses were not associated with better outcomes or clinical seizure cessation in response to second‐line medications in these benzodiazepine‐refractory seizures. Significance Benzodiazepines as first‐line treatment of SE, particularly midazolam and lorazepam, are frequently underdosed throughout the United States. This broad and generalizable cohort confirms prior single site reports that underdosing is both pervasive and difficult to remediate. (ESETT ClinicalTrials.gov identifier: NCT01960075.)

Status epilepticus: Practice variation and adherence to treatment guideline in a large community hospital

“…To save time and maximize efficacy, the therapeutic dose should be given as a single dose whenever possible. Underdosing of benzodiazepines, or failure to initiate drug treatment altogether, are frequent problems during the early treatment of SE [20,21]. In our cohort, 43.9% of the starting doses of an IV benzodiazepine drug were lower than the lowest guideline-recommended dose.…”

Persistent Underdosing of Benzodiazepines for Status Epilepticus: The Weight Is the Hardest Part

“…Despite these efforts to improve guideline compliance among 460 subjects enrolled from 57 US hospitals, only 1 in 3 received a first benzodiazepine dose that was within the minimum recommended range. 5 As with the prior report, most patients received 2-3 doses of benzodiazepine, each lower than recommended. Lorazepam was primarily given intravenously in the emergency department, but only 24% of doses were within guidelines.…”

“…Disappointingly, this updated examination of the appropriateness of benzodiazepine administration for out-of-hospital status found little interval improvement. 5 The authors again looked at dosing of benzodiazepine as a first line for status epilepticus in an updated cohort of children and adults enrolled in ESETT through 2018. After the gap in benzodiazepine dosing was observed in the initial cohort, the investigators state they redoubled their efforts to educate study sites on evidence-based best practices.…”

“… 4 Thus, prior to the current analyses, they provided updated instruction to site investigators on the guidelines as well as tools to increase guideline compliance. 5 This disappointing outcome should not discourage further efforts to educate emergency medical service providers and physicians who treat status epilepticus but does invite consideration of what other barriers are present.…”

Management of status epilepticus: a narrative review

“…Availability, adequate dosing and speed of administration are more important than which benzodiazepine is used. Despite the strong evidence base for their use, under-dosing of benzodiazepines is widespread [24]. Contrary to popular belief, administration of adequate doses of first-line benzodiazepines has been shown to decrease the requirement for tracheal intubation [25].…”