Inadequate benzodiazepine dosing may result in progression to refractory and non‐convulsive status epilepticus

Rao, Shishir; Mahulikar, Advait; Ibrahim, Mohammad; Shah, Aashit; Seraji‐Bozorgzad, Navid; Mohamed, Wazim

doi:10.1684/epd.2018.0987

Cited by 14 publications

(11 citation statements)

References 16 publications

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“…When analyzing results from all 460 patients who failed first-line therapy, we observed a pattern of administering multiple, smaller than recommended benzodiazepine doses in the EMS and ED settings, which confirms and extends the findings from our previous analysis of the first 200 unique enrollments 14 and is consistent with other reports. [6][7][8][9][10][11][12][13] With regard to route of administration and setting, MDZ was primarily administered intramuscularly or intravenously by EMS personnel, whereas LZP was almost exclusively dosed intravenously in the ED. These patterns are in general agreement with published literature.…”

Section: Discussionmentioning

confidence: 99%

“…Underdosing of benzodiazepines as first-line treatments have been reported in several previously published reports [6][7][8][9][10][11][12][13] and pointed to an association with poor response. 9,10,12,13 However, these reports typically involved fewer than three sites, small sample size, and limited characterization of use patterns. The recently completed ESETT, with its large number of sites across the United States and detailed information about first-line therapy offered the opportunity to characterize patterns of benzodiazepine use prior to enrollment in the trial.…”

Section: Introductionmentioning

confidence: 92%

“…Underdosing of benzodiazepines as first‐line treatments have been reported in several previously published reports 6–13 and pointed to an association with poor response 9,10,12,13 . However, these reports typically involved fewer than three sites, small sample size, and limited characterization of use patterns.…”

Section: Introductionmentioning

confidence: 99%

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Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial

et al. 2021

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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.)

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 92%

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Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial

et al. 2021

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“…On admission and at discharge we collected the number of prescribed medications; the number, molecules and dosages of BZRA ( Appendix 1 ); and the number and molecules of other psychotropic drugs (N02A, N03A, N04, N05A, N05C, N06A-C-D). BZRA dosages were converted into lorazepam-equivalent doses using a conversion table [ 30 , 31 ], so that molecules could be compared at baseline and between admission and discharge. Polypharmacy was defined as regular use of 5 or more drugs [ 32 ] and excessive polypharmacy as use of 10 or more drugs [ 33 ].…”

Section: Methodsmentioning

confidence: 99%

Current practice in benzodiazepine receptor agonists deprescribing on acute geriatric wards: a cohort study

et al. 2022

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Background Benzodiazepine receptor agonist (BZRA) use is highly prevalent in hospitalised older people although these drugs are associated with numerous and serious adverse events. Deprescribing can reduce risks associated with chronic BZRA use. The aim of this study was to measure the prevalence of, and factors associated with, BZRA deprescribing in acute geriatric units. Methods During a one-year period, this multicentre retrospective study included patients aged ≥70 years, hospitalised in acute geriatric units, and using ≥1 BZRA on admission. BZRA deprescribing at discharge was defined as: ≥25% decrease in lorazepam-equivalent admission dose; discontinuation of all BZRAs; or cessation of a rescue prescription at discharge. BZRA cessation was defined as discontinuation of all BZRAs at discharge. We identified social, medical, geriatric and medication factors associated with BZRA deprescribing using logistic regression. Results In total, 561 patients were included (mean age: 85.3±5.9 years, 70% of women). BZRA deprescribing occurred in 240 (42.8%), including 85 with BZRA cessation (15.2%). Deprescribing occurred more frequently in patients with a BZRA-related adverse event on admission or during hospital stay (odds ratio (OR) 4.5; 95% confidence interval [2.6; 7.9]), with an antidepressant (1.6 [1.1; 2.4]) and a higher lorazepam-equivalent dosage on admission (OR 1.2 [1; 1.4]), and less frequently in patients with antipsychotic drug (OR 0.5 [0.3; 0.8]). BZRA cessation was more likely in patients with a BZRA-related adverse event (OR 2.2 [1.2; 4.3]) and a lower lorazepam-equivalent dosage on admission (OR 0.5 [0.3; 0.6]). Conclusions During hospitalisation in the acute geriatric units of our hospital, BZRA deprescribing occurred in 42.8% of the patients. Identification of an BZRA-related adverse event by the treating physician appears to be a major factor: this reactive deprescribing accounted for 74% of cases in our study. Further prospective studies are needed to measure long-term persistence of in-hospital deprescribing and encourage proactive management.

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“…A retrospective study demonstrated that adequate benzodiazepine dosing in SE was uncommon (only 31%), and that inadequate benzodiazepine dosing strategies were associated with progression to RSE. 51…”

Section: Lorazepammentioning

confidence: 99%

Acute Provoked Seizures—Work-Up and Management in Adults

Moosavi

Swisher

2020

Semin Neurol

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Acute provoked seizures, also known as acute symptomatic seizures, occur secondary to a neurological or systemic precipitant, commonly presenting as a first-time seizure. In this article, we will discuss etiology, emergent protocols, medical work-up, initial treatment, and management of these seizures. The definitions, classifications, and management of convulsive status epilepticus and nonconvulsive status epilepticus in an acute setting will also be reviewed.

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Inadequate benzodiazepine dosing may result in progression to refractory and non‐convulsive status epilepticus

Cited by 14 publications

References 16 publications

Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial

Patterns of benzodiazepine underdosing in the Established Status Epilepticus Treatment Trial

Current practice in benzodiazepine receptor agonists deprescribing on acute geriatric wards: a cohort study

Acute Provoked Seizures—Work-Up and Management in Adults

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